Implant material and process for producing the same

ABSTRACT

The present invention provides an implant material comprising an organic-inorganic complex porous article and a production method thereof. The organic-inorganic complex porous article is a biodegradable and bioabsorbable bioactive porous article in which a bioactive bioceramics powder is uniformly dispersed in a biodegradable and bioabsorbable polymer, wherein it has continuous pores and the bioceramics powder is partly exposed to the pore inner surface or the pore inner surface and the porous article surface.

TECHNICAL FIELD

This invention relates to an implant material comprising a bioactive anddegradable and absorbable organic-inorganic complex porous article and aproduction method thereof, and an implant material comprising thiscomplex porous article and other biomaterial.

BACKGROUND OF THE INVENTION

As inorganic porous articles to be used for clinical purposes, forexample, porous ceramics obtained by calcining or sintering bioceramicsare known. However, since such porous ceramics show a disadvantage ofbeing hard but friable when used in applications such as a scaffoldingfor living bone tissue reconstruction, a prosthetic material and thelike, there always is a danger of causing destruction by a slight impactafter the operation. Also, it is difficult to process and change theshape of porous ceramics to match to the shape of the damaged part of aliving bone tissue in the field of operation, too. In addition, since 10years or more of a prolonged period of time is required in some casesuntil it is completely replaced by a living bone, a danger of causingharmful effects by its destruction remains during this period.

On the other hand, as organic porous articles to be used for clinicalpurposes, for example, a sponge and the like disclosed in JP-B-63-64988are known. This sponge is generally used for the blood stanching at thetime of surgical operation or as a prosthetic material at the time ofthe suture of a soft tissue (e.g., an organ) in the living body, whichis a sponge having continuous pores comprising a biodegradable andbioabsorbable polylactic acid. Such a sponge is produced by a method inwhich polylactic acid is dissolved in benzene or dioxane, and thesolvent is sublimed by freeze-drying the polymer solution.

However, regarding a porous article produced by a freeze drying methodsuch as the case of the above sponge, it is difficult to remove thesolvent completely because it requires a prolonged period of time forthe sublimation, and since it has a thin thickness of 1 mm or less(generally about several hundred μm), it is difficult in reality toproduce a porous article having a thickness of several mm or more. Asother methods for producing porous articles having continuous pores,various methods have been examined in addition to the aforementionedfreeze drying method, but it is not easy to obtain a thick porousarticle of several mm or more. It is impossible to apply such a thinporous article in compliance with the shape of, for example, a complexand relatively large three dimensional space of a damaged part of aliving body tissue, thereby allowing it to exert its function as atemporal prosthetic material and simultaneously effecting threedimensional tissue reconstruction of the damaged part. Accordingly,there is a demand for those which has thickness, and can be made into athree dimensional cube before or during an operation, and are degradedand absorbed and replaced by a living bone at a relatively early stage.

Also, an elution method is known as another reliable method for making aporous article having continuous pores, in which a large amount of awater-soluble powder having a certain size such as NaCl is mixed with apolymer, and the mixture is formed into a sheet or the like thin moldingand then soaked in water (solvent) to effect elusion of said powder,thereby forming continuous pores having the same diameter of saidpowder, but since it is difficult to elute said powder completely, theproducts are limited to thin article of continuous pores. Also,continuous pores can hardly be obtained when ratio of the water-solublepowder becomes high. What is more, when this porous article is embeddedinto the living body, it causes a problem of being encumbered with thetoxicity of said powder still remaining.

Like the case of the aforementioned sponge, a porous article which doesnot contain bioactive bioceramics and the like inorganic powders islacking direct bindability, conductivity, replaceability and the likewith bone, cartilage and the like bone tissues in the living body, sothat not osteoblast but fibroblast and the like soft tissues arepenetrated and present therein, thus requiring a considerably prolongedperiod of time until the bone tissue in the living body is completelyreplaced and regenerated, or it ends up un-replaced.

Accordingly, the present applicant has already applied for a patent on athick porous article having continuous pores comprising a biodegradableand bioabsorbable polymer, wherein a bioactive bioceramics powder iscontained inside thereof, which becomes a scaffold of a threedimensional cube when osteoblast is inoculated and can be transplantedinto a damaged part of a large bone for mediation (Japanese PatentApplication No. 8-229280).

This porous article is produced by a porous article production methodcalled solution precipitation method. That is, by a method in which asuspension is prepared by dissolving a biodegradable and bioabsorbablepolymer in a mixed solvent of its solvent with a non-solvent having aboiling point higher than that of the solvent and simultaneouslydispersing a bioceramics powder therein, and the bioceramicspowder-including biodegradable and bioabsorbable polymer is precipitatedby evaporating the mixed solvent from this suspension at a temperaturelower than the boiling point of the solvent.

The principle for forming a porous article by this solutionprecipitation method is as follows. That is, when the mixed solvent isevaporated from the aforementioned suspension at a temperature lowerthan the boiling point of the solvent, ratio of the non-solvent havinghigher boiling point is gradually increased by preferential evaporationof the solvent having lower boiling point, and the solvent becomesunable to dissolve the polymer when the solvent and non-solvent reach acertain ratio. Because of this, the polymer starts its deposition andprecipitation and includes the bioceramics powder which is starting itsprecipitation from the beginning, the thus deposited and precipitatedpolymer is shrunk and solidified by the high ratio non-solvent and fixedwhile including the bioceramics powder, and a cell structure in whichthe mixed solvent is included is formed on the connected thin cell wallsof the polymer. Thereafter, the remaining solvent evaporates anddisappears while making pores by destroying parts of the cell walls, andthe non-solvent having higher boiling point also evaporates graduallythrough said pores and completely evaporates and disappears in the end.As a result, a bioceramics powder-containing porous article is formed,in which remains of the mixed solvent reservoirs included in the polymercell walls are connected as continuous pores.

The aforementioned solution precipitation method is an epoch-makingmethod which can form a thick porous article having from a low expansionratio to a high expansion ratio, and it is possible to obtain ablock-shaped three dimensional porous article having a thickness of fromseveral mm to several ten mm. Accordingly, this is markedly useful for,e.g., a scaffold of the regeneration of a solid shape (three dimensionalsolid shape) bone having large relief.

However, this method has a disadvantage in that a bioceramics powderbelonging to a relatively large particle diameter among the particlediameter distribution in a suspension containing the bioceramics powderin a large amount starts its precipitation from the beginning of thesolvent evaporation, and a fairly large amount of the bioceramics powderis already starting its precipitation with a density gradient toward thebottom when the polymer starts its deposition and precipitation, so thatthe bioceramics powder content of the thus obtained porous article isnot uniform as a whole and it is not avoidable therefore that thecontent increases from the upper side toward the bottom side of theporous article. Such a heterogeneous porous article having a densitygradient of the content cannot be used efficiently and indiscriminatelyfor its applications such as a scaffold for bone tissue reconstruction,a prosthetic material, a bone filler and the like. It is possible toimprove such a problem to a certain degree by controlling sedimentationvelocity and the like of the bioceramics powder by a certain method, butit cannot be solved completely. Particularly, it is difficult, not onlyby the invention but in general, to prepare a porous article for threedimensional bone reconstruction use containing 30% by weight or more ofa bioceramics powder and having a homogeneous and uniform concentration.

Regarding the porous article having a small content of bioceramicspowder produced by the aforementioned method, the majority of thebioceramics powder is included in the polymer cell wall and can hardlybe exposed to the inner face of the continuous pores and the surface ofthe porous article, so that it has a problem in that when embedded inthe living body, conduction action of a living bone tissue by thebioceramics powder can hardly be exerted from just after the embedding,and the bioactivity therefore is exhibited having a time lag togetherwith the bioceramics powder exposed at the same time with thedegradation of the polymer which forms a skin layer.

Also, even when extremely fine particles are selected as the bioceramicspowder, its percentage content in the porous article produced by theaforementioned method is up to about 30% by weight at the most, and whenit is contained in an amount larger than this, the bioceramics powderbecomes more apt to precipitate so that the bottom side of the thusobtained porous article contains a large amount of the bioceramicspowder and therefore becomes extremely brittle.

In addition, the porous article produced by the aforementioned methodgenerally has continuous pores in a large occupying ratio of 80% ormore, but in generally saying, only continuous pores having a relativelysmall pore diameter of from several μm to several ten μm are obtained sothat it cannot always say that the pore diameter and pore shape idealfor the penetration and proliferation of osteoblast into and in theporous article are formed.

Methods for highly filling inorganic powder substances have beenexamined by other methods than the aforementioned solution precipitationmethod of the present applicant, and one of the influential methodsamong them is a method for preparing an article of continuous pores by abaking method in which granules are prepared by filling a polymer withabout 50% by weight of a bioceramics powder, and these particles arefused on the surface by heating. This method is not a brand-new methodbut well known as a method for preparing a porous article of a granularresin such as an epoxy resin, a vinyl chloride resin or the like. Sincethis method requires surface fusion, the filling amount has a limitationand 50% by weight or more of filing is hard to achieve due to generationof brittleness, and control of the pore diameter is not easy too, sothat a product having good quality can hardly be obtained.

The invention aims at providing various implant materials comprising anorganic-inorganic complex porous article highly filled with inorganicparticles, which can resolve all of these problems, and productionmethods thereof. In addition, it also contemplates providing implantmaterials comprising combinations of this organic-inorganic complexporous article with other living body materials, which are used as bonefixing materials, used as vertebral body fixing materials[intervertebral installation material and vertebral body prostheticmaterial] and the like, used as substitutes for bone allograft, boneautograft, cortical bone, spongy bone or combinations thereof, used asprosthetic and filling materials and the like for defect parts anddeformed parts of bones, used as scaffolds for bone and cartilageformation, and used as artificial cartilage.

Currently, a bone fixing material such as a fixing pin comprising abiodegradable and bioabsorbable polymer is used, which is embedded bybridging the marrow of both sides of an incised part of the sternum, forexample, in the surgical operation of sternum splitting incisionclosing. Since this is gradually degraded and absorbed in the sternum,it has an advantage of not requiring its extraction from the living bodyby carrying out re-operation like the case of pins made ofnon-absorbable ceramics or metals, but since it has no bone conductionand does not directly bind to a bone tissue, it merely has an effect toclose the incised face through provisional fixing of the closed sternumby exerting an action as a simple “wedge”. Because of this, when thespongy bone becomes brittle by changing into a wafer retaining only athin cortical bone as can be seen in the majority of the sternum of theaged, it causes problems in that even when this fixing pin for thesternum is embedded, it is difficult to increase fixing stability byexerting its action as the “wedge” and it is not replaced by a bonetissue. On the other hand, porous articles of hydroxyapatite (HA) andthe like ceramics, which are used for the connection and fixation of cutregions and fractured regions of bones other than the sternum, haveproblems in that they are apt to break and require a considerablyprolonged period of time to be absorbed in the living body. Though thereis an opinion that there is no problem even when a prolonged period oftime is required, because its strength is restored once embedded in theliving bone, but there still is a danger of causing breakage until it iscompletely embedded. The implant materials of the invention to be usedas bone fixing materials mainly aim at resolving these problems.

In this connection, a conventional vertebral body fixing material suchas a cage made of titanium or carbon to be used as an intervertebralspacer in the anterior interbody fusion for lumbar spine degenerationdiseases satisfies chemical biocompatibility of the surface for thepresent, but since dynamical biocompatibility is different from theliving body, there are problems such as a danger of exhibiting harmfuleffect on the peripheral tissues by periodical breakage and corrosiondue to its protracted presence as a foreign matter in the living body.For example, there is a problem in that the cage subsides into thevertebral body via a osseous endplate exposed by reaming, generated dueto disharmony of dynamical characteristics between the cage and theliving body. Particularly, being hard but brittle, a cage made of carbonis broken along its carbon fibers and generates fine pieces in somecases, so that a possibility of exhibiting harmful effect thereby alwaysremains. Also, a bone for autograft to be filled in these cages isgenerally supplied by extracting an ilium, but there are a problemregarding its amount and preparation and a problem in terms ofcomplicated treatments after the extraction (after treatment of theextracted region, and pulverization, filling in the cage, treatmentunder sterile condition and the like of the ilium). The implantmaterials of the invention to be used as vertebral body fixing materialsmainly aim at resolving these problems.

On the other hand, an operation for making up defect parts of bones isusually carried out in recent years making use of a bone allograftprepared by cutting and processing a cadaveric bone or a bone autograftextracted from a region of a large bone such as the pelvis, a rib or thelike. When the bone allograft is in a block shape integrated byproviding a cortical bone on the surface of a spongy bone, a corticalbone region of a defect position of a bone can be made up by thecortical bone of said allograft, a spongy bone region of a defectposition of a bone can be made up by the spongy bone of said allograft.However, since the bone allograft is prepared by cutting and processinga cadaveric bone, it poses a problem in that it is not easy to providenecessary and sufficient amount of graft bone by obtaining the materialcadaveric bones in a large amount, and it also poses a problem in thatworkable shapes are greatly limited. Also, even in the case of a boneallograft, the transplanted said graft bone is a bone tissue differentfrom its own bone tissue, there is a possibility that it disappears byits spontaneous absorption and its strength becomes insufficient or isreduced, depending on the embedding conditions. In addition to this, itis necessary to carry out a sterilization treatment because it is acadaveric bone of other person, but since denaturation of the cadavericbone occurs depending on its conditions, it is necessary to controlsufficient sterilization conditions. However, since it is insufficientsometimes, there is a case in which generation of a serious accidentextending to death is announced after its embedding. Though such anaccident can be avoided by a bone autograft extracted during anoperation, it cannot be denied that its amount is insufficient. On theother hand, embedding of implant materials made of hydroxyapatite (HA),tricalcium phosphate (TCP) and the like bioactive ceramics are alsocarried out at a defect part, but in that case, there is a problem inthat a cortical bone region and a spongy bone region of a defectposition of a bone are evenly made up by the hard ceramics, and sincesuch ceramics remain semipermanently, it still poses a problem of beingnot able to reconstruct the defect position of bone by a self bonetissue. Thus, a method for obtaining a substitution for the spongy boneby preparing porous articles of said ceramics is becoming considerablyrealistic. However, since it is the best ideally that these syntheticartificial bones are replaced by living bones, when they are replacedafter a prolonged period of 10 to 20 years, an accident as a physicalforeign matter during this period must be feared in sometimes. Theimplant materials of the invention to be used as substitutes for boneallograft and bone autograft mainly aim at resolving these problems.

In addition, a punching (mesh shape) plate made of titanium or the likemetal in which a large number of pores are formed by punching, a punchedflat plate or rugged plate comprising a compact article or porousarticle of baked bioceramics, and the like, are used as conventionalprosthetic, filling and coating materials of defect parts and deformedparts of bones. However, since the punching plate made of a metal lacksin physical biocompatibility and remains permanently as a foreign matterin the made-up region, there is a danger of exhibiting harmful effect onthe peripheral tissues caused by corrosion, metal ion elution and thelike during its long-term embedding, so that there is a problem in thatthe defect parts cannot be completely replaced at all by a bone tissue.In addition, since the porous article of baked bioceramics is hard butbrittle and easily broken, there is a danger of being broken byreceiving impact during its use and there is a problem in that it cannotbe post-formed during an operation to match the three dimensional shapeof the defect part of bone. The implant materials of the invention to beused as prosthetic, filling, coating and the like materials mainly aimat resolving these problems.

In addition, a conventional artificial cartilage, for example, a totalreplacement type independent artificial intervertebral disk is anartificial intervertebral disk having a so-called sandwich structure inwhich two metal endplates made of titanium or cobalt-chromium aresuperposed on both sides (upside and down side) of a core comprisingbio-inactive polyethylene or a rubber having biocompatibility, whereinthe core portion performs a movement similar to that of the livingintervertebral disk depending on the superposing condition of the twosheets of polyethylene and, in the case of a rubber, it is imitated byits elasticity. In order to give effect of its independence bypreventing slipping when inserted between vertebral bodies, it is madeinto a structure in which several horns are projected on the surface ofthe metal plate so that they are fixed by sticking into concave of thevertebral body. However, since this artificial intervertebral disk has asandwich structure of materials having different qualities from those ofthe living body, it has great disadvantages in that abrasion is formedbetween their interface after repetition of movement, it cannot be saidby no means that the movement is the same as that of the livingintervertebral disk, and the horns projected from the metal plate notonly injure the upper and lower vertebral bodies but also cause stillmore damages by gradually subsiding and penetrating into the vertebralbodies during its use for a prolonged period of time, so that it cannotbe independently fixed by directly binding to the upper and lowervertebral bodies. The implant material of the invention to be used as anartificial cartilage mainly aims at resolving these problems, and byintervening the porous article of the invention between vertebral bodiesincluding the endplate, it also aim at effecting close contact byfilling a physical gap with said artificial intervertebral disk, andalso at effecting direct bonding with the vertebral body by the boneconduction.

DISCLOSURE OF THE INVENTION

The most basic implant material of the invention comprises anorganic-inorganic complex porous article which is a biodegradable andbioabsorbable bioactive porous article in which a bioactive bioceramicspowder is uniformly dispersed in a biodegradable and bioabsorbablepolymer, wherein it has continuous pores and the bioceramics powder ispartly exposed to the pore inner surface or the pore inner surface andthe porous article surface. As will be described later, this porousarticle has a porosity of from 50 to 90%, the continuous pores occupyfrom 50 to 90% of the total pores, and the continuous pores arecontrolled at a pore size of approximately from 100 to 400 μm which issuitable for the penetration, proliferation and stabilization ofosteoblast. In addition, the bioceramics powder is contained in a largeamount of from 60 to 90% by weight, and the porous article has a threedimensional solid shape having a large thickness of from 1 to 50 mm.This basic implant material is used in various clinical applicationssuch as a scaffolding for substitution type bone tissue regeneration, aprosthetic material, a coating material, a bone filler, a substitute forspongy bone, an inclusion between a bone tissue and other artificialimplant, a drug carrier and the like.

In addition, an implant material comprising an organic-inorganic complexwhich is a biodegradable and bioabsorbable bioactive porous article inwhich a bioactive bioceramics powder is uniformly dispersed in abiodegradable and bioabsorbable polymer, wherein it has continuous poresand a bioceramics powder percentage content of from 60 to 90% by weight,is also a basic implant material of the invention and used in variousclinical applications similar to the above.

The above implant material comprising an organic-inorganic complexporous article can be produced by a production method of the invention,namely a method in which a nonwoven fabric-like fiber aggregate isformed from a mixed solution prepared by dissolving a biodegradable andbioabsorbable polymer in a volatile solvent and dispersing a bioactivebioceramics powder therein, this is formed into a porous fiber aggregatemolding by compression-molding it under heating, the fiber aggregatemolding is soaked in the volatile solvent, and then said solvent isremoved.

On the other hand, the implant materials of the invention to which theaforementioned organic-inorganic complex porous article is applied areobtained by uniting the aforementioned organic-inorganic complex porousarticle with other compact biodegradable and bioabsorbable member. Thefollowing four kinds are the main types of such implant materials.

The first implant material is an implant material for bone fixation inwhich the other biodegradable and bioabsorbable member is a pin, whereinsaid pin is united by penetrating through the aforementioned porousarticle, and both termini of the pin are stuck out from theaforementioned porous article. This implant material is suitably used,for example, for fixing the sternum split and incised in surgicaloperation of sternum splitting incision closing.

The second implant material is an implant material in which the otherbiodegradable and bioabsorbable member is a matrix having a cavityopening into the outside and comprising a biodegradable andbioabsorbable polymer containing a bioactive bioceramics powder, whereinthe aforementioned porous article is united by packing in the cavity ofsaid matrix and the aforementioned porous article is partly exposed fromsaid matrix. This implant material is suitably used as an intervertebralspacer or the like vertebral body fixing material in the anterior orposterior interbody fusion and the like.

The third implant material is an implant material in which the otherbiodegradable and bioabsorbable member is a skin layer comprising abiodegradable and bioabsorbable polymer containing a bioactivebioceramics powder, wherein said skin layer is united by superposing ona part of the surface of the aforementioned porous article in a blockshape. In this implant material, the block-shaped porous article takes arole of the spongy bone and the skin layer takes a role of the corticalbone, so that it is suitably used as total absorption substitution typeartificial bones such as substitutes for bone allograft, bone autograftand the like.

The fourth implant material is an implant material in which the otherbiodegradable and bioabsorbable member is a net-shaped body comprising abiodegradable and bioabsorbable polymer containing a bioactivebioceramics powder, wherein the aforementioned porous article is unitedby packing in the mesh of said net-shaped body. This implant material issuitably used as a prosthetic, coating, supporting or filling materialand the like of defect parts and deformed parts of bones.

In addition, still another implant material of the invention appliedwith the aforementioned porous article is an implant material forartificial cartilage, in which the aforementioned porous article isunited by laminating the aforementioned porous article on at least oneside of a core material comprising a texture structure body prepared byconverting organic fibers into a multi-axial three dimensional weavetexture or knit texture of three axes or more or a complex texturethereof. This implant material is suitably used as artificialintervertebral disk, meniscus and the like which are independently fixedby directly binding to the upper and lower vertebral bodies.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective illustration showing an embodiment of theimplant material according to the invention.

FIGS. 2( a), (b) and (c) are explanatory drawings showing applicationexamples of the implant material of the same embodiment.

FIG. 3 is a perspective illustration showing another embodiment of theimplant material according to the invention.

FIG. 4 is a perspective illustration showing a matrix of the implantmaterial of the same embodiment.

FIG. 5 is a longitudinal sectional view showing the implant material ofthe same embodiment.

FIG. 6 is an explanatory drawing showing an application example of theimplant material of the same embodiment.

FIG. 7 is a perspective illustration showing still another embodiment ofthe implant material according to the invention.

FIG. 8 is a perspective illustration showing still another embodiment ofthe implant material according to the invention.

FIG. 9 is a perspective illustration showing still another embodiment ofthe implant material according to the invention.

FIG. 10 is a perspective illustration showing still another embodimentof the implant material according to the invention.

FIG. 11 is a sectional view showing the implant material of the sameembodiment.

FIG. 12 is an explanatory drawing showing an application example of theimplant material of the same embodiment.

FIG. 13 is a sectional view showing still another embodiment of theimplant material according to the invention.

FIG. 14 is a sectional view showing still another embodiment of theimplant material according to the invention.

FIG. 15 is a sectional view showing still another embodiment of theimplant material according to the invention.

FIG. 16 is a perspective illustration showing still another embodimentof the implant material according to the invention.

FIG. 17 is a sectional view showing the implant material of the sameembodiment.

BEST MODE FOR CARRYING OUT THE INVENTION

The following illustratively describes desirable embodiments of theimplant materials of the invention and production methods thereof.

The most basic implant material of the invention comprises anorganic-inorganic complex porous article which is a biodegradable andbioabsorbable bioactive porous article in which a bioactive bioceramicspowder is uniformly dispersed in a biodegradable and bioabsorbablepolymer, wherein it has continuous pores and the bioceramics powder ispartly exposed to the pore inner surface or the pore inner surface andthe porous article surface, and in its desirable embodiment, a polymerwhich is already put into practical use by confirming its safety,degraded relatively quickly and not brittle when the porous article isformed is selected and used as the biodegradable and bioabsorbablepolymer. That is, amorphous or crystalline/amorphous-mixed totallyabsorbable poly-D,L-lactic acid, a block copolymer of L-lactic acid withD,L-lactic acid, a copolymer of lactic acid with glycolic acid, acopolymer of lactic acid with p-dioxanone, a copolymer of lactic acidwith ethylene glycol, a copolymer of lactic acid with caprolactone, amixture thereof and the like biodegradable and bioabsorbable polymersare used. A polymer having a viscosity average molecular weight of from50,000 to 1,000,000 is preferably used by taking into consideration easyformation of the nonwoven fabric-like fiber aggregate in the productionmethod of the invention and period of degradation and absorption of theporous article in the living body.

Particularly, poly-D,L-lactic acid, a block copolymer of L-lactic acidwith D,L-lactic acid, a copolymer of lactic acid with glycolic acid, acopolymer of lactic acid with p-dioxanone and the like biodegradable andbioabsorbable polymers which show amorphous nature based on the monomerratio are desirable from the viewpoint of solvent characteristics when anonwoven fabric-like fiber aggregate is formed in accordance with theproduction method of the invention and when a porous fiber aggregatemolding formed by compression-molding this under heating is treated witha volatile solvent, and the use of these polymers renders possiblepreparation of an implant material comprising an organic-inorganiccomplex porous article, which is not brittle even when a large amount ofbioceramics powder is contained, has a compressive strength equivalentto that of spongy bone, can be heat-deformed at a relatively lowtemperature (about 70° C.) different from the case of porous articles ofceramics alone, and is quickly hydrolyzed and completely absorbed after6 to 12 months in the living body. An implant material having suchcharacteristics is markedly desirable as a material for filling a defectpart of a living bone, and being a complex body, it also maintainsthermoplastic resin-specific advantages in that it maintainsviscoelasticity by the resin component different from the case of amaterial of ceramics alone, it does not cause breakage unlike the caseof ceramics due to brittleness when merely touched, and its shape can beadjusted to match with a defect part during an operation byheat-deforming it.

Since molecular weight of a biodegradable and completely bioabsorbablepolymer exerts influence upon the period until it is hydrolyzed andcompletely absorbed and the possibility of fiber formation, a polymerhaving a viscosity average molecular weight of from 50,000 to 1,000,000is used as described in the foregoing. A polymer having a viscosityaverage molecular weight of smaller than 50,000 has a short period oftime until hydrolyzed into an oligomer or monomer unit having lowmolecular weight, but being insufficient in spinnability, it isdifficult to form a fiber aggregate while forming fibers by spraying orthe like means in accordance with the production method of theinvention. Also, a polymer having a viscosity average molecular weightof larger than 1,000,000 requires a long period of time until completelyhydrolyzed, so that it is unfit for the polymer of complex porousarticles when early stage replacement by a living bone tissue is theobject. Though it varies depending on each polymer, its desirableviscosity average molecular weight is from 100,000 to 300,000, and whena biodegradable and bioabsorbable polymer having a molecular weightwithin this range is used, formation of the fiber aggregate becomeseasy, and an implant material of complex porous article havingappropriate hydrolysis complete period can be obtained.

Also, in the implant material comprising an organic-inorganic complexporous article, a powder having a bioactivity and good bone conduction(occasionally showing bone induction) and good biocompatibility is usedas the bioceramics powder to be dispersed in the porous article.Examples of such a bioceramics powder include powders of calcined orsintered hydroxyapatite, apatite wollastonite glass ceramics, bioactiveand completely bioabsorbable un-calcined or un-sintered hydroxyapatite,dicalcium phosphate, tricalcium phosphate, tetracalcium phosphate,octacalcium phosphate, calcite, ceravital, diopside, natural coral andthe like. In addition, those which are prepared by adhering an alkalineinorganic compound, a basic organic compound and the like on the surfaceof these powders can also be used. Because of the reason that tissueregeneration carried out by total substitution by a self bone tissue isideal, a completely bioabsorbable bioceramics powder which is completelyabsorbed and completely replaced by a bone tissue in the living body isdesirable among them, and un-calcined or un-sintered hydroxyapatite,tricalcium phosphate and octacalcium phosphate are particularlydesirable because they have large activities, are excellent in boneconduction, have low harmful effect due to excellent biocompatibilityand are absorbed in the living body during a short period of time.

It is desirable to use the aforementioned bioceramics powder having anaverage particle size (average particle size of primary particles) offrom 0.2 to 10 μm, because when a bioceramics powder having a particlesize larger than this is used, it becomes difficult to form a fiberaggregate due to cutting of fibers into short pieces when a mixedsolution prepared by mixing said powder is splayed and made into fibersby the production method of the invention, and even in case that a fiberaggregate can be formed, there is a possibility that the bioceramicspowder is slightly precipitated and dispersed unevenly before the fibersare solidified. Those having a size exceeding 20 to 30 μm are notdesirable, because even they are completely absorbable, a prolongedperiod of time is required for their complete absorption, and tissuereactions during that period are exhibited occasionally.

More preferred particle size of bioceramics powder is from 0.2 to 5 μm,because when such a bioceramics powder is used, fibers are hardly cutout in case that a fiber aggregate is formed by making a mixed solutionprepared by mixing high concentration of said powder in the productionmethod of the invention into fine fibers having a fiber diameter of from1 to 3 μm, and when it is in a high concentration like the case of theinvention, said powder is included in fibers under a condition of beingexposed from the fibers so that the fiber aggregate after its soakingtreatment with a volatile solvent becomes a complex porous article inwhich said powder is exposed from the surface or inner surface of thecontinuous pores.

In the case of an implant material comprising an organic-inorganiccomplex porous article, which is used for clinical applications such asa scaffold in regeneration medical engineering, a carrier or bone fillerfor DDS, a substitute for a heteromorphic spongy bone (bone allograft)and the like, it is desirable to control percentage content of thebioceramics powder within the range of from 60 to 90% by weight from theviewpoint of bioactivity of the bioceramics. When a complex porousarticle is prepared by forming an aggregate of fibers containing abioceramics powder and soaking, in a volatile solvent, a fiber aggregatemolding prepared by compression-molding under heating, like the case ofthe production method of the invention, a large amount of thebioceramics powder can be contained within such a range that it ispossible to form fibers, so that percentage content of the bioceramicspowder can be increased to a level of from 60 to 90% by weight (volume %when a powder having an average particle size of 3 μm and a specificgravity of 2.7 is used corresponds to a high ratio of approximately from41 to 81%) as described in the above. In case that the percentagecontent of bioceramics powder exceeds 90% by weight, formation of afiber aggregate becomes difficult because satisfactory fibers cannot beobtained due to their cutting into short pieces when fiber formation iscarried out, and when it is less than 60% by weight on the other hand,the bioceramics powder is insufficient and hardly exposed to thesurface, so that the bioactivity originated from the bioceramics powderis hardly exhibited from the early stage after embedding of the implantmaterial into the living body.

Such a complex porous article which enabled to uniformly disperse abioactive bioceramics powder in a high percentage content of from 60 to90% by weight in this manner cannot be found in the prior art and is oneof the basic implant materials of the invention.

Desirable volume % of the bioceramics powder is from 50 to 85% byvolume. This volume % is a percentage of the volume of the bioceramicspowder to the volume of the polymer in case that porosity of the polymerin the complex porous article is 0%, and the volume % changes dependingon the specific gravity and average particle size of the bioceramicspowder even when weight of the bioceramics powder is constant.Accordingly, taking specific gravity and average particle size of thebioceramics powder into consideration, it is desirable to contain it atfrom 50 to 85% by volume. More desirable volume % is from 50 to 80% byvolume.

Since porous ceramics obtained by sintering hydroxyapatite and the likeceramics are hard but brittle, thin materials are easily broken orchipped by an external force and not satisfactory as implants. Contraryto this, a complex porous article prepared by including a bioceramicspowder particularly in an amorphous biodegradable and bioabsorbablepolymer has a compressive strength equivalent to that of the spongy bonewhich keeps flexibility and is not brittle, illustratively a compressivestrength of approximately from 1 MPa to 5 MPa, by the binding effect ofthe polymer even when the bioceramics powder has a high percent contentof from 60 to 90% by weight, so that it can be suitably used for asubstitute for spongy bone and other clinical applications as has beenalready described. In this connection, the aforementioned compressivestrength is a value measured using an autograph AGS-2000D manufacturedby Shimadzu, based on the test method of JIS K 7181 (however, the sizeof each sample was fixed to 10×10×15 mm, and the compression speed to 5mm/min).

An implant material comprising this organic-inorganic complex porousarticle has a porosity (total porosity) of 50% or more, which can beincreased to about 90% technically, but when both of the physicalstrength of this complex porous article and penetration andstabilization of osteoblast are taken into consideration, it isapproximately from 60 to 80%, and when the penetrating efficiency ofosteoblast into the central part of the complex porous article is takeninto consideration, it is desirable that the continuous pores occupy 50to 90%, particularly 70 to 90%, of the total pores.

Pore size of the continuous pores of this organic-inorganic complexporous article is set to approximately from 100 to 400 μm. Studies onthe pore size of porous ceramics and penetration and stabilization ofosteoblast have already been carried out many times, and it has beenrevealed based on the results that a pore size of from 300 to 400 μm ismost effective for calcification and the effect is diluted as departingfrom this range. Thus, though the pore size of this complex porousarticle is set to a value of approximately from 100 to 400 μm asdescribed in the foregoing, those having a pore size within the range offrom 50 to 500 μm are included, and the distribution center may be from200 to 400 μm.

In this connection, when pore size of the continuous pores is largerthan 400 μm and porosity (total porosity) is higher than 90%, strengthof the complex porous article is reduced so that it is highly possibleto cause its breakage during embedding in the living body. On the otherhand, when the pore size is smaller than 100 μm and the porosity islower than 50%, strength of the complex porous article is improved butthe period until its hydrolysis and complete absorption is prolongedbecause penetration of osteoblast becomes difficult. However, such a lowporosity complex porous article having small pore size can be used insome cases as a material from which retaining of sustained releaseproperty is required for a relatively prolonged period of time inparallel with the degradation of the polymer as a carrier of DDS. Morepreferred pore size of the continuous pores is from 150 to 350 μm, andmore preferred porosity (total porosity) is from 70 to 80%. In thisconnection, the pore-size of continuous pores and the ratio ofcontinuous pores occupying total pores can be controlled by adjustingthe compressibility when a fiber aggregate is formed into a fiberaggregate molding by its compression molding in the production method ofthe invention or by adjusting the external pressure for shape-keepingwhen the fiber aggregate molding is soaked in a volatile solvent whilekeeping its shape.

The aforementioned implant material comprising an organic-inorganiccomplex porous article is used, for example, by embedding it into adefect part of a living bone, and in that case, the implant material canbe embedded without a gap in the defect part by deforming it into ashape matching the defect part through its heating at about 70° C.making use of thermoplastic property of the biodegradable andbioabsorbable polymer, so that it becomes possible to carry out theembedding operation simply and accurately. In addition, due to thetoughness possessed by the biodegradable and bioabsorbable polymer andthe hardness of ceramics powder, it is possible to use it by cuttinginto an optional shape without loosing the shape using a surgical knifeduring an operation.

When an implant material comprising this complex porous article isembedded into a defect part of a living bone as described in the above,humor are quickly permeated into inside of the complex porous articlefrom the surface of the complex porous article through the inside ofcontinuous pores, so that hydrolysis of the biodegradable andbioabsorbable polymer progresses almost simultaneously from both of thesurface of the complex porous article and the inside of the continuouspores, and the degradation progresses uniformly over the entire porousarticle. In addition, due to the bone conduction ability of thebioceramics powder exposing on the surface of the complex porousarticle, a bone tissue is quickly conducted and formed on the surfacelayer of the complex porous article and grows as a small column of bone,and the complex porous article binds to the defect part of living bonewithin a short period of time, and also due to the bone conductionability of the bioceramics powder exposing inside of the pores, the bonetissue penetrates also into inside of the complex porous article andeffect conduction and growth of osteoblast so that it directly binds tothe peripheral bone. This phenomenon becomes significant accompanied bythe progress of degradation of the biodegradable and bioabsorbablepolymer, and it is gradually substituted with the peripheral bone.Finally, the polymer is completely degraded and absorbed and thecompletely absorbable bioceramics powder is also completely absorbed,and regeneration of the defect part of bone is completed throughcomplete replacement by the grown bone tissue.

Wettability of this implant material comprising the complex porousarticle in the living body is considerably improved than that of aporous article of a biodegradable and bioabsorbable polymer alone, dueto the wettability of the bioceramics powder contained in a large amountand exposed on the surface, but wettability of the polymer is alsoimproved when corona discharge, plasma treatment, hydrogen peroxidetreatment or the like oxidation treatment is applied to this complexporous article, so that penetration and growth of the osteoblast to beproliferated can be carried out further effectively.

In addition, when various types of ossification factors, growth factors,drugs and the like are included by filling them in pores of the complexporous article in advance or dissolving in the biodegradable andbioabsorbable polymer in advance, they are gradually released inresponse to the degrading and absorbing rate of the complex porousarticle, so that regeneration of bones and healing of diseases can beaccelerated and effected. The main ossification factor includes BMP, andexamples of the main growth factors include IL-1, TNF-α, TNF-β, IFN-γand the like monokine and lymphokine, or colony-stimulating factor, orTGF-α, TGF-β, IGF-1, PDGF, FGF and the like so-called proliferationdifferentiation factors. Also, drugs which are concerned in the growthof bones (vitamin D, prostaglandins, anti-tumor (carcinostatic) agentsand the like), antimicrobial agents and the like can be optionallyselected as the drugs.

Next, the method of the invention for producing an implant materialcomprising an organic-inorganic complex porous article is illustrativelydescribed in detail.

According to the production method of the invention, the aforementionedbiodegradable and bioabsorbable polymer is dissolved in a volatilesolvent, and a mixed solution is prepared by uniformly dispersing theaforementioned bioceramics powder therein. As the volatile solvent,dichloromethane, dichloroethane, methylene chloride, chloroform or thelike low boiling point solvent which is apt to evaporate at atemperature slightly higher than the ordinary temperature can be used.It is also possible to use are volatile mixed solvents prepared bymixing these solvents with one or two or more of non-solvents havingboiling points higher than these solvents, such as methanol, ethanol,1-propanol, 2-propanol, 2-butanol, ter-butanol, ter-pentanol and thelike alcohols having a boiling point within the range of from 60 to 110°C.

Next, a nonwoven fabric-like fiber aggregate is prepared from the abovemixed solution. As its means, a means for making fibers by spraying thedissolved mixed solution is preferably used. That is, when theaforementioned dissolved mixed solution is charged in a sprayer and themixed solution is sprayed to a substance from the injection nozzle ofthe sprayer with nitrogen gas or the like inert high pressure injectiongas, fibers are formed while the volatile solvent is evaporated, andfibers of the biodegradable and bioabsorbable polymer containing thebioceramics powder are aggregated, solidified and accumulated bymutually entwining and adhering at their contacting points, therebyeffecting formation of a thick nonwoven fabric-like fiber aggregate ofan optional shape. Though shape of the inter-fiber gap is different froma cell-shape pore, this fiber aggregate forms continued spaces ofapproximately several hundred μm between the adhered and solidifiedfibers, and the bioceramics powder is included in the fibers (partlyexposing on the surface) and uniformly dispersed over all of the fiberaggregate molding.

For the purpose of making such a resin containing a bioceramics powderin a large amount of 60% by weight or more (sometimes 50% volume ormore) into a material in which this is fixed by solidifying under auniformly dispersed state without causing precipitation and separationand it also contains continuous gaps as pores inside thereof, it isreasonable to use a means for evaporating a solvent while forming thinfibers by a spraying system and effecting their solidification within ashort period of time before separation of the bioceramics powder, likethe case of this production method, and a novelty of the productionmethod of the invention also resides therein.

In this connection, in order to obtain a complex porous article havingan extremely thick thickness of from 5 to 50 mm which is necessarysometimes as an implant material for clinical use, a predeterminedthickness may be obtained by forming this fiber aggregate by sprayingand then, after its drying by evaporation of the solvent, againrepeating a step of thickening it by spraying thereon.

As the aforementioned substance to be injected, a net or platecomprising a polyethylene or the like olefinic resin, a fluorine resin,a silicon resin or the like having good releasing ability is used.Particularly, when a net or the like substance to be injected havingfree aeration is used, the mixed solution is formed into fibers by itsspraying and hit the net and then the volatile solvent is evaporatedthrough the mesh, so that it has advantages in that a fiber aggregatecan be formed without generating a skin layer (adhered layer of theresin alone) by fusion of fibers on the surface of the net side, and apermeation treatment of the solvent in the subsequent step can be easilycarried out. A net having a mesh of from 50 to 300 is desirable, becausea net having a mesh of larger than 50 meshes causes turning of fibersinto the backside through the mesh and therefore entails in a difficultyin releasing the formed fiber aggregate from the net, and a net having amesh of smaller than 300 meshes cannot perform smooth evaporation of thevolatile solvent so that the net side fibers are apt to fuse and form askin layer. In this connection, the substance to be injected is notlimited to a flat net or plate, and a convex-curved and/orconcave-curved three dimensional net or plate may also be used. The useof such a three dimensional substance to be injected has an advantage inthat a fiber aggregate having a thickness identical to the threedimensional shape can be formed.

The fiber aggregate formed by making fibers by spraying the mixedsolution as described in the above has a large inter-fiber gap ofseveral hundred μm, and the ratio of inter-fiber gaps (porosity) isapproximately from 60 to 90%. In addition, since the inorganic particlesare contained in fibers and do not precipitate, they are uniformlydispersed over entire part of the fiber aggregate.

It is desirable that the fiber length of this fiber aggregate isapproximately from 3 to 100 mm, and it is desirable that the fiberdiameter is approximately from 0.5 to 50 μm. A fiber aggregate havingsuch degrees of fiber length and fiber diameter is convenient forobtaining a complex porous article from which fibers are substantiallydisappeared through easy fusion of the fibers by the subsequent step forpermeation treatment of the solvent.

The fiber length mainly depends on the molecular weight of thebiodegradable and bioabsorbable polymer, polymer concentration of themixed solution, percentage content and particle size of the bioceramicspowder and the like, and there is a tendency that the fiber lengthbecomes long as the molecular weight becomes large, the polymerconcentration becomes high, the percent content of bioceramics powderbecomes small and the particle size of bioceramics powder becomes small.On the other hand, the fiber diameter mainly depends on the polymerconcentration of the mixed solution, percentage content of thebioceramics powder, size of the injection nozzle of the sprayer and thelike, and there is a tendency that the fiber diameter becomes thick asthe polymer concentration becomes high, the percentage content ofbioceramics powder becomes large, and the size of injection nozzlebecomes large. In addition, the fiber diameter is also changed by thepressure of injection gas. Accordingly, in order to obtain theaforementioned fiber length and fiber diameter, it is necessary tocontrol molecular weight of the polymer, polymer concentration,percentage content and particle size of the bioceramics powder, size ofthe injection nozzle, gas pressure and the like.

Next, a subsequent step is carried out for forming a porous fiberaggregate molding by compression-molding the aforementioned fiberaggregate under heating. Firstly, preliminary moldings having continuedvoids are prepared by solidifying the fiber aggregate under heating andcompression, and the preliminary moldings are subjected to compressionmolding under higher pressure than the former, thereby obtaining aporous fiber aggregate molding having a strength and controlled ratio ofcontinued voids and pore size. In this case, the heating at the time ofcompression molding is such a degree that the fiber aggregate isslightly softened, and the compression is controlled at such a degreethat porosity of the finally obtained complex porous article becomesfrom 50 to 90% and pore size of the continuous pores becomes roughlyfrom 100 to 400 μm.

By further moving to the next step, the fiber aggregate molding obtainedin the previous step is soaked in the aforementioned volatile solvent toeffect sufficient permeation of said solvent into inside of the molding.Thereafter, this solvent is removed. When the fiber aggregate molding issoaked in the volatile solvent, the fiber aggregate molding is packed ina mold with a face having a large number of pores and soaked whilemaintaining the shape under such a condition that an appropriatepressure is added to the fiber aggregate molding from the outside.Alternatively, the solvent may be permeated by pouring it on the uppersurface of the fiber aggregate molding. In addition, in order tomaintain a desired shape, it is desirable to remove the solvent quicklyby a method in which the solvent inside of the fiber aggregate moldingis vacuum-suctioned.

When the fiber aggregate molding is soaked in the volatile solvent toallow the solvent to permeate into the molding, the fibers are fusedwith one another while the fibers contract by dissolving in the solventfrom the surface, and the fibers substantially disappear to form afoamed membrane. Thereafter, a foamed wall is formed under such a statethat continued round pores having a gap pore size of approximately from100 to 400 μm are remained, and its shape is changed to a body ofcontinuous pores. A part of the bioceramics powder contained in thefibers in a large amount is included inside of the pore membrane (insidethe foamed wall) accompanied by the fusion of fibers and morphologicalchanges by membrane formation, without causing precipitation, and a partthereof is exposed from the pore membrane and also exposed on the porousarticle surface by embedding in such a degree that said powder does noteasily fallout. However, there is a case in which a skin layer is formedon the surface depending on the conditions so that the bioceramicspowder is not exposed on the porous article surface, and in that case, atreatment for exposing the inorganic powder present in the surface layerthrough removal of the skin layer by sanding may be carried out.

In this manner, it is possible to obtain an implant material comprisingan organic-inorganic complex porous article having continuous pores, inwhich a large amount of a bioceramics powder is uniformly dispersed anda part of the bioceramics powder is exposed to the inner side of poresand the porous article surface. According to this complex porousarticle, the average pore size of continuous pores can be controlled atapproximately from 100 to 400 μm which is convenient for the penetrationand stabilization of osteoblast, and the porosity can also be controlledat approximately from 50 to 90%, by controlling external pressure forkeeping shape of the fiber aggregate molding when it is soaked in thevolatile solvent. In this connection, when the soaking treatment of thefiber aggregate molding in the volatile solvent is carried out underheating at from 50 to 60° C., fibers are sufficiently fused with oneanother by merely allowing the fiber aggregate molding as it is for ashort period of time so that the complex porous article can be obtainedefficiently.

According to the production method of the invention, it is possible tocontain a bioceramics powder uniformly in the complex porous article inan amount of from 60 to 90% by weight (corresponds to 41 to 81% byvolume in the case of unbaked hydroxyapatite having an average particlesize of 3 μm and a specific gravity of 2.7) within such a range thatfibers can be formed, and even when contained in a large amount, thesolvent is evaporated and the fibers are adhered before the bioceramicspowder is precipitated and separated, so that a high percentage contentcomplex porous article in which the bioceramics powder is uniformlydispersed in comparison with the porous article obtained by theaforementioned solution precipitation method, which could not so farbeen obtained, can be finally obtained. However, there is an upperlimitation, because when the percentage content is too high, amount ofthe biodegradable and bioabsorbable polymer as a binder becomes small,and the complex porous article becomes brittle and keeping of its shapetherefore becomes difficult.

EXAMPLES

Next, further illustrative embodiments of the implant material of theinvention comprising an organic-inorganic complex porous article aredescribed.

Example 1

By uniformly homogenizing a polymer solution prepared by dissolvingpoly-D,L-lactic acid (PDLLA) (molar ratio of D-lactic acid and L-lacticacid, 50/50) having a viscosity average molecular weight of 200,000 indichloromethane (concentration: PDLLA 4 g/dichloromethane 100 ml) and asuspension prepared by suspending unbaked hydroxyapatite powder (u-HApowder) having an average particle size of 3 μm in ethanol, a mixedsolution in which 230 parts by weight of u-HA powder is mixed with 100parts by weight of PDLLA was prepared.

Using HP-E Air Brush (mfd. by Anest Iwata) as a sprayer, the abovesuspension was charged into this and sprayed on a polyethylene net (150mesh) at about 120 cm distance by 1.6 kg/cm² pressure nitrogen gas toform a fiber aggregate, and the fiber aggregate was released from thenet. Fiber diameter of this fiber aggregate was about 1.0 μm, its fiberlength was approximately from 10 to 20 mm, and its apparent specificgravity was 0.2.

This fiber aggregate was cut into an appropriate size, packed into acylindrical female die of 30 mm in diameter and 30 mm in depth andcompressed with a male die such that apparent specific gravity of thefiber aggregate became 0.5, thereby obtaining a disc shape fiberaggregate molding having a diameter of 30 mm and a thickness of 5 mm.

Next, this fiber aggregate molding was soaked in a solvent comprisingethanol-mixed dichloromethane to effect permeation of said solvent intoinside of the molding, and after allowing it to stand at 60° C. for 10minutes, the solvent in the inner part of the molding was removed byvacuum suction to obtain an organic-inorganic complex porous articlehaving a diameter of 30 mm, a thickness of 4 mm and a u-HA powderpercentage content of 70% by weight.

When a partial section of this complex porous article was observed underan electron microscope, the fibers were fused and disappeared,continuous pores having a large pore size of from 100 to 400 μm wereformed, the u-HA powder was uniformly dispersed, and a part of the u-HApowder was exposed to the inner face of the pores and the porous articlesurface. Apparent specific gravity of this complex porous article was0.5, the ratio of continuous pores occupying total pores (continuousporosity) was 75%, and the compressive strength was 1.1 MPa.

Example 2

A disc shape fiber aggregate molding having a diameter of 30 mm and athickness of 5 mm was prepared as a preliminary molding in the samemanner as in Example 1, and this was heated to 80° C. in a geer oven,put into a chamber equipped with a diameter reducing part in which itsdiameter is gradually reduced, and then press-fitted into a cylinderhaving a bottom part diameter of 10.6 mm. The cylindrical rod-shapedfiber aggregate molding compression-molded under heating in this mannershowed a compressive strength of about 2.5 MPa.

Next, this cylindrical rod-shaped fiber aggregate molding was put into acylinder of the same diameter having holes on its periphery and soakedfor 10 minutes in a solvent (60° C.) comprising 15% by weightmethanol-mixed dichloromethane, while pressing it by applying a pressurefrom its upper side and lower side to such a degree that height of thecylindrical rod-shaped fiber aggregate molding did not change, and thensaid solvent was removed to obtain a complex porous article.

When a partial section of this complex porous article and its surfaceafter sanding were observed under an electron microscope, it had afiber-disappeared porous shape, its pore size was comprised of mixedpores of approximately from 150 to 300 μm, and the u-HA powder wasexposed from the porous article surface and the inner face of the pores.Apparent specific gravity of this complex porous article was about 0.55,the continuous porosity was 70%, and the compressive strength wasincreased to about 3.5 MPa. Judging from the viscosity average molecularweight of PDLLA and the ratio of its occupying amount and the in vivobiodegradable and bioabsorbable characteristics of the u-HA powderhaving an average particle size of 3 μm, it is considered that thiscomplex porous article is completely absorbed after a period of fromabout 6 months to 12 months, though it depends on its embedded regionand size.

Example 3

A mixed solution was prepared by synthesizing PDLLA (molar ratio ofD-lactic acid and L-lactic acid, 30/70) having a viscosity averagemolecular weight of 100,000 and uniformly mixing it with 80% by weightof a β-tricalcium phosphate powder (β-TCP powder) having an averageparticle size of about 3 μm by the same method of Example 1. It has beenconfirmed that this β-TCP powder is bioactive and absorbable in theliving body and, though the mechanism is different from the u-HA powder,it is known that this shows a bone conduction ability to form HA in theliving body.

Using this mixed solution, a fiber aggregate prepared by the sprayingmethod in the same manner as in Example 2 was made into a fiberaggregate molding by carrying out compression molding under heating, andthis was subjected to a solvent soaking treatment to obtain a complexporous article having an apparent specific gravity of about 0.6, acontinuous porosity of 75% and a compressive strength of 4.2 MPa. Sincevolume ratio of the β-TCP powder of this complex porous article is about65% by volume, the volume ratio of the β-TCP powder is considerablylarger than the case of the complex porous articles of Examples 1 and 2containing 70% by weight (about 55% by volume) of the u-HA powder, sothat the bioactivity is significantly exhibited by the exposure of theβ-TCP powder to the surface and pore inner face of the porous article.

It was confirmed that, since this complex porous article was changed toa shape due to disappearance of fibers of the nonwoven fabric-like fiberaggregate, in which the β-TCP powder is embedded into the bulky cellwalls dispersion of this powder into the peripheral caused bydisintegration hardly occurs even when soaked in the humors in theliving body, and it is completely degraded and absorbed within 5 to 8months while showing good bioactivity. Accordingly, this complex porousarticle becomes a good scaffold for hard tissues (bone and cartilage).

Example 4

D,L-lactic acid (D/L molar ratio, 1) was mixed with glycolic acid (GA)at a molar ratio of 8:2, and a copolymer P (DLLA-GA) having a viscosityaverage molecular weight of 130,000 was synthesized by a known method.By preparing a mixed solution in which this polymer was uniformly mixedwith 60% by weight of an octacalcium phosphate powder (OCP powder), afiber aggregate prepared by the spraying method in the same manner as inExample 2 was made into a fiber aggregate molding by carrying outcompression molding under heating, and this was subjected to a solventsoaking treatment to finally obtain a complex porous article having anapparent specific gravity of 0.50. Since activity of the OCP powder washigh and degradation and absorption of the copolymer were quick due toGA, the majority of this complex porous article was absorbed andreplaced by a bone after 3 to 4 months showing good bone conduction(aptness to change to a new bone).

Example 5

D,L-lactide was mixed with para-dioxanone (p-DOX) at a molar ratio of8:2, and a copolymer having a viscosity average molecular weight ofabout 100,000 was synthesized by carrying out their copolymerization bya known method. Though a volatile general purpose good solvent for thepolymer of p-DOX could not be found, it was soluble in chloroform,dichloromethane and the like at the aforementioned ratio, so that it wasable to obtain the object complex porous article by the same method ofExample 1. Also, since the aforementioned copolymer shows a rubber-likeproperty having higher plasticity than that of the D,L-lacticacid/glycolic acid copolymer P (DLLA-GA) of Example 4, volume ratio ofthe bioceramics powder when particle size of said powder is 3 μm can beincreased to 70% by volume (85% by weight), so that this complex porousarticle can avoid reactions in the living body caused by the degradationproducts of the copolymer to the utmost, and activity of the bioactivebioceramics powder is exhibited markedly effectively. Particularly,since its hydrophilic nature is higher than that of PDLLA due tocharacteristics of p-DOX, it is considered that this complex porousarticle is effective as a scaffold or the like for the regeneration ofcartilage in proliferating cells by ex vivo (in vitro dish).

As has been described in the foregoing, since the implant material ofthe invention comprising an organic-inorganic complex porous articlecontains a bioceramics powder in a biodegradable and bioabsorbablepolymer in a large amount under uniformly dispersed condition, a humorand the like quickly permeate through the large pore size continuouspores formed inside thereof, so that binding with a living bone andregeneration of a living bone tissue can be effected at an early stageby bone conduction of the bioceramics powder exposed to the porousarticle surface and the inner face of continuous pores, and it has apractical strength necessary for clinical applications and can beproduced easily and accurately by the production method of theinvention. Accordingly, as described in the foregoing, this implantmaterial is practically used as a scaffolding for the reconstruction ofliving bone tissue, a prosthetic material, a bone filler, an inclusionbetween other implant and a living bone tissue, a substitute for spongybone, a carrier for sustained drug release and the like.

Next, typical embodiments of the implant material in which theaforementioned organic-inorganic complex porous article of the presentinvention is applied are described in detail with reference to thedrawings. Such an implant material is roughly divided into a type inwhich the aforementioned porous article is united with other compactbiodegradable and bioabsorbable member and another type in which theaforementioned porous article is united with a bio-non-absorbablemember, and various embodiments shown in FIG. 1 to FIG. 15 can beexemplified as main cases of the former implant material, and theembodiments shown in FIG. 16 and FIG. 17 as main cases of the latterimplant material.

The implant material 10 shown in FIG. 1 is an implant material forfixing median incision closed sternum, as a typical example of thebioactive and biodegradable and bioabsorbable implant material forfixing a bone, which is embedded when a bone of a region where trabeculabecame rough and thin caused by the reduction of the bone or atrophy ofthe bone tissue due to osteoporosis is incised or cut or when a defectpart of a bone is closed and connected by a surgical operation.

This implant material 10 has an organic-inorganic complex porous article1 and a pin 2 as a biodegradable and bioabsorbable member, the pin 2passes through the porous article 1, and both termini of the pin areprojected from said porous article 1. In addition, in order to preventrevolution when embedded in a sternum, the pin 2 is formed into aprismatic shape and the porous article 1 is formed into a rectangularprism shape. Also, in order to facilitate insertion into a hole formedin the marrow of the sternum (spongy bone), both termini of the pin 2are formed into a pyramidal shape, and in order to prevent slipping ofthe pin 2 from the just described hole, a concavo-convex structure 2 ahaving a saw tooth-like section is formed on the surface of the bothtermini of this pin 2. In this connection, the pin 2 may be formed intoa columnar shape, and the porous article 1 into a cylindrical shape, andthe concavo-convex structure 2 a of both termini of the pin may beomitted.

The porous article 1 is the same as the aforementioned organic-inorganiccomplex porous article, namely a biodegradable and bioabsorbable porousarticle having continuous pores, in which a bioactive bioceramics powderis substantially uniformly dispersed in a biodegradable andbioabsorbable polymer, wherein a part of the bioceramics powder isexposed to the inner face of the pores or the inner face of the poresand the porous article surface. With respect to this porous article 1,porosity, pore size of the continuous pores, ratio of the continuouspores occupying the total pores, the biodegradable and bioabsorbablepolymer, the bioceramics powder, percentage content of said powder andthe like are as described in the foregoing.

This porous article 1 is prepared in accordance with the aforementionedproduction method, by forming a porous fiber aggregate molding throughcompression molding of a nonwoven fabric-like fiber aggregate into arectangular prism shape under heating, and punching a square hole forpin 2 insertion (a square hole having a size slightly smaller than thepin 2) on the rectangular prism shape organic-inorganic complex porousarticle obtained by soaking this molding in a volatile solvent.

The dimensions of this porous article 1 can be selected in response toeach clinical case, and though the size is not particularly limited, itis necessary to pay attention so that it does not become too large(many). In the case of an implant material for sternum fixing, it isdesirable to set length of the porous article 1 to approximately from 10to 15 mm, and its width to approximately from 6 to 20 mm, and its heightto approximately from 6 to 15 mm. It is needless to say that itsselection within this range depends on the structure of sternum of eachpatient. When each dimension of the porous article 1 is smaller than thelower limit of the aforementioned range, bone tissues to be conductedand formed on the porous article 1 becomes less. In this connection, itis needless to say that preferred dimensions of this porous article 1also change in response to each embedding bone.

Functional effects of this porous article 1 can be increased bycontaining the aforementioned ossification factors, growth factors,drugs and the like in an appropriate amounts. When an ossificationfactor or a growth factor is contained, ossification is considerablyaccelerated in the porous article 1 so that the porous article 1 issubstituted with a bone tissue at an early stage and both of the incisedand closed half-sternum parts are directly bonded. Also, when it isimpregnated with a drug, the drug is directly absorbed into both of thehalf-sternum parts so that sufficient drug effect is exerted. Inaddition, it is desirable to effect penetration and proliferation ofosteoblast more effectively by improving wettability through theapplication of the aforementioned oxidation treatment to the surface ofthis porous article 1.

On the other hand, the aforementioned pin 2 comprises crystallinepolylactic acid, polyglycolic acid and the like biodegradable andbioabsorbable polymers whose safety has been confirmed, andparticularly, a high strength pin 2 comprising a biodegradable andbioabsorbable polymer having a viscosity average molecular weight of150,000 or more, preferably approximately from 200,000 to 600,000, issuitably used. Also can be used suitably are a pin comprising a complexbody in which approximately from 10 to 60% by weight of theaforementioned bioactive bioceramics powder is mixed with thesebiodegradable and bioabsorbable polymers, and a pin whose strength isfurther improved through the orientation of molecules and crystals ofthe aforementioned polymers by compression molding, forged molding,stretching or the like method. Particularly, those which have a compactquality obtained by orientating polymer molecules and crystals in threedimensional directions by a forged molding are suitably employed.

In the case of an implant material for sternum fixing, it is desirablethat length of the pin 2 is approximately from 20 to 40 mm, because lessthan 20 mm is too short as a pin for sternum fixing, and when longerthan 40 mm, on the other hand, it causes an inconvenience in that thepin can hardly be put into the marrow of sternum (spongy bone). Also, itis desirable that width of the pin 2 is approximately from 2 to 4 mm,and it is desirable that its height is approximately from 2 to 3 mm.When width of the pin 2 is narrower than 2 mm and its height is smallerthan 2 mm, it becomes so thin that the pin 2 would break, and when widthof the pin 2 is broader than 4 mm and its height is larger than 3 mm, onthe other hand, it cannot be used because its combination with theporous article 1 exceeds thickness of the sternum. In this connection,the dimensions of the aforementioned pin are desirable dimensions in thecase of an implant material for sternum fixing to the utmost, and it isneedless to say that desirable dimensions of the pin change in responseto the embedding bone.

Next, using examples of the aforementioned implant material 10 forsternum fixing are described with reference to FIG. 2.

Firstly, as shown in FIG. 2(A), two steel wires 3 and 3 are insertedinto median-incised right and left half-sternum parts B and B using apick, and a binding tape 4 is wrapped around the half-sternum parts Band B through the intercostal space. Though only one tape of thisbinding tape 4 is wrapped in FIG. 2(A), two or more tapes (generallyfour) are wrapped by vertically keeping spaces. Then, two or more ofhole 5 (a hole having a size slightly smaller than the implant material10) into which a one side half of the implant material 10 for sternumfixing can be inserted are formed by scraping out with a Kocher clamp orthe like unnecessary spongy bones of both of the half-sternum parts Band B.

Next, as shown in FIG. 2(B), one side half of the implant material 10 isinserted into each hole 5 of the one side half-sternum part B by firmlypushing it so that it does not slip out. Then, as shown in FIG. 2(C),both of the half-sternum parts B and B are closed by pulling the steelwires 3 and 3 and thereby pushing the opposite side half of each of theimplant material 10 into each hole 5 of the other half-sternum part B,distal parts of the wires 3 and 3 are firmly ligated by adding severalknots, and each binding tape 4 is also firmly ligated by adding severalknots at the same time. In this connection, though the steel wire 3 andbinding tape 4 are used in this embodiment for fixing the half-sternumparts B and B, a band formed from a biodegradable and bioabsorbablepolymer such as the aforementioned polylactic acid or from a mixture ofthis polymer with a bioceramics powder can also be used.

When the implant material 10 for sternum fixing is embedded in themarrow of an incised and closed sternum as described in the above, inthe initial stage after embedding, pin 2 of the implant material 10sticks as a “wedge” into the marrow (spongy bone) of both of thehalf-sternum parts B and B to exert a reinforcing action by fixing bothof the half-sternum parts B and B, so that fixing stability of both ofthe half-sternum parts is improved. In addition, effected by the boneconduction ability of the bioceramics powder exposing on the surface ofthe porous article 1 of this implant material 10, a bone tissue isconducted and formed on the surface of the porous article 1, and theporous article 1 and both of the half-sternum parts B and B are bondedwithin a short period, so that fixing stability and strength of thehalf-sternum parts B and B are improved by this bonding too.

According to this implant material 10, hydrolysis of the pin 2 andporous article 1 progresses by their contact with humors in the marrow,but the porous article 1 is hydrolyzed more quickly because humorspenetrate into its inner part through the continuous pores, and what ismore, since a bone tissue is conducted and formed in the inner part bythe bone conduction ability of the bioceramics powder exposing to theinner surface of the pores, this porous article 1 is replaced by thebone tissue and disappears within a relatively short period of time.Particularly, when the porous article 1 is impregnated with theaforementioned growth factor, growth of the bone tissue is quick and theporous article 1 is replaced by the bone tissue within a short period.Accordingly, since the closed sternum (half-sternum parts B and B) isdirectly bonded by the bone tissue substituted with the porous article1, fixing of the sternum is stabilized by the newly formed bone even incase that the spongy bone of an osteoporosis sternum bone becomesextremely hollow and porous and thereby forms a wafer state and becomesbrittle.

On the other hand, hydrolysis of the pin 2 of the implant material 10gradually progresses by its contact with humors and significantlyprogresses at the time when the porous article 1 is replaced by a bonetissue, and the porous article becomes fine pieces soon thereafter andfinally disappears by completely absorbed by the living body. In thatcase, when the pin 2 comprises the aforementioned complex body of abiodegradable and bioabsorbable polymer and a bioceramics powder, thepin 2 also shows bone conduction ability, so that a bone is conductedand formed by the repetition of its hydrolysis and replacement ofosteoblast and osteoclast by the bioceramics powder, the pin 2 isreplaced by the bone tissue accompanied by the phagocytic reaction ofdegraded fine pieces, and the hole where the pin 2 was stuck into isfinally filled with a neoplastic bone and disappears.

The implant material 10 of the invention for bone fixation comprisingorganic-inorganic complex porous article 1 and pin 2 is not only used byembedding it in a sternum incised and closed by a sternum medianincision closing operation as described in the above, but also used byembedding it when a bone of a region where trabecula became rough andthin caused by the reduction of the bone or atrophy of the bone tissuedue to osteoporosis is incised or cut or when a defect part of a bone isclosed and connected by a surgical operation, and can firmly connect andfix a bone by finally replaced by the bone tissue.

As shown in FIG. 6, the implant material 11 shown in FIG. 3 is used asan intervertebral spacer or the like vertebral body fixing material,mainly by inserting between cervical vertebrae C₃ and C₄ or betweenlumbar vertebrae L₄ and L₅. This implant material 11 comprises anorganic-inorganic complex porous article 1 and a matrix 6 which is abiodegradable and bioabsorbable member equipped with a cavity 6 aopening toward the outside, and the porous article 1 is set in thecavity 6 a of the matrix 6 and partly exposed from an inlet 6 b of saidcavity 6 a, and the porous article 1 is also arranged on the upper andlower sides of the matrix 6 by superposing in a plate shape. The porousarticle 1 on the upper and lower sides of the matrix 6 is used as asubstitute for an auto-bone and, as will be described later, arranged tofacilitate early stage binding (fixation) by getting rid of the gapbetween the matrix 6 and the cervical vertebrae C₃ and C₄ or the lumbarvertebrae L₄ and L₅. In this case, the porous article 1 on the upper andlower sides of the matrix 6 can be omitted.

The matrix 6 of this implant material 11 is a compact matrix havingstrength comprising a biodegradable and bioabsorbable polymer containinga bioactive bioceramics powder and, as shown in FIG. 4, formed into arectangular prism shape. Two lengthwise through perforating cavities 6 aand two crosswise through perforating cavities 6 a, opening toward theoutside, are formed on this matrix 6 in a mutually crossing manner, andinlets 6 b of these cavities 6 a are opened in pairs on all four sidesof the matrix 6. The inlets 6 b of these cavities 6 a are used as thepenetrating inlets for humors and the like, and the porous article 1 setinto each of the cavities 6 a is partly exposed from each inlet 6 b. Inthis connection, it is possible to form the inlet 6 b of cavity 6 a onthe front face and rear face of the matrix 6, too, and in that case, itis desirable to form the rear face inlet into a screw hole shape so thatthe tip of an insertion jig can be screwed into it.

In order to facilitate insertion of this implant material 11 into thegap between the cervical vertebrae C₃ and C₄ or between the lumbarvertebrae L₄ and L₅, four edges of the front face 6 c of the matrix 6are chamfered. Also, in order to make the implant material 11 into anindependent type (not requiring an auxiliary fixing material) which doesnot cause displacement and removal after its insertion into the gapbetween the cervical vertebrae C₃ and C₄ or between the lumbar vertebraeL₄ and L₅, several (6 for each in the drawing) projections 6 f forfixation are arranged on both upper and lower faces 6 d and 6 e of thematrix 6, and the tip part of each projection 6 f is stuck out from theporous article 1 of the upper and lower faces of the matrix 6. As shownin FIG. 4, this projection 6 f is prepared by forming a concave hole 6 gon the upper and lower faces of the matrix 6, and putting a pin 6 h (6f) having a pointed conical tip and comprising the same biodegradableand bioabsorbable polymer of the matrix 6 into the concave hole 6 g. Inthis connection, a stabbing piece or the like having a sharp tip may beused instead of the pin 6 h, and the projection 6 f and the matrix 6 maybe formed integrally.

As shown in FIG. 5, a communication hole 6 j is formed on a wall part 6i between the two lengthwise cavities 6 a and 6 a of the matrix 6 sothat, as will be described later, a bone tissue to be conducted andformed on the porous articles 1 and 1 set into the cavities can beconnected through the communication hole 6 j. This wall part 6 i istaking a role in increasing compressive strength of the matrix 6.

Regarding the size of matrix 6, its fore and aft dimension isapproximately from 18 to 30 mm, and its above and below height dimensionand right and left width dimension are approximately from 6 to 24 mm,and when those having various sizes are assorted within these ranges, amatrix fitted to the size of the cervical vertebrae C₃ and C₄ or thelumbar vertebrae L₄ and L₅ and to the intervertebral dimension can beselected and inserted.

In the matrix 6 of this implant material 11, the lengthwise andcrosswise cavities 6 a are formed into a through hole shape havingracetrack section, but they may be formed into through hole shapeshaving square, circular, oval and the like various sections. Inaddition, it is possible to make the entire inner portion of the matrix6 into a hollow chamber-like cavity and to effect communication of thecavity with the outside by forming inlet of said cavity on all fourfaces of the matrix 6.

In this connection, the cavity 6 a passing through the matrix 6 in thecrosswise direction can be omitted, because when the cavity 6 a passingthrough it in the lengthwise direction is present, a bone tissue isconducted and formed from the upper and lower cervical vertebrae C₃ andC₄ or lumbar vertebrae L₄ and L₅ and fused and fixed to the porousarticle 1 set in its inside. In addition, the inlets 1 b on the rightand left two sides of the matrix 6 can also be omitted.

The aforementioned matrix 6 comprises a biodegradable and bioabsorbablepolymer containing a bioactive bioceramics powder, and the polymersusing the pin 2 of the aforementioned implant material 10, namelycrystalline poly-L-lactic acid, polyglycolic acid and the like whosesafety in the living body has been confirmed are desirably used as thematerial biodegradable and bioabsorbable polymer, and particularly, ahigh strength matrix 6 prepared using poly-L-lactic acid having aviscosity average molecular weight of 150,000 or more, preferablyapproximately from 200,000 to 600,000, is suitable. Such a matrix 6 isproduced by a method in which a material biodegradable and bioabsorbablepolymer is subjected to injection molding or a molded block of thematerial biodegradable and bioabsorbable polymer is subjected to cuttingwork. In the latter method, a matrix 6 obtained by subjecting a moldedblock to a compression molding, forged molding or the like means to forma block in which the polymer molecules and crystals are oriented andthen subjecting this to cutting work is markedly suitable, because ithas a compact quality and its strength is further improved due to thethree dimensionally oriented polymer molecules and crystals. In additionto this, a block prepared by stretch-molding as a molded block can alsobe used suitably, and it is also desirable to increase its strength bycarrying out a cutting work in such a manner that the stretchingdirection (orientation direction) becomes lengthwise.

As the bioceramics powder to be contained in this matrix 6, all of theaforementioned bioactive totally absorbable bioceramics powders can beused, and similar to the case of the aforementioned pin 2 of implantmaterial 10, it is desirable to control its percentage content at from10 to 60% by weight. Formation of bone conduction by the bioceramicspowder becomes insufficient when it is less than 10% by weight, and thematrix 6 becomes fragile when it exceeds 60% by weight.

On the other hand, the porous article 1 to be filled in the cavity 6 aof the matrix 6 is identical to the aforementioned organic-inorganiccomplex porous article, namely a biodegradable and bioabsorbable porousarticle having continuous pores, in which a bioactive bioceramics powderis substantially uniformly dispersed in a biodegradable andbioabsorbable polymer, wherein a part of the bioceramics powder isexposed to the inner face of the pores or the inner face of the poresand the porous article surface. With respect to this porous article 1,porosity, pore size of the continuous pores, ratio of the continuouspores occupying the total pores, the biodegradable and bioabsorbablepolymer, the bioceramics powder, percentage content of said powder andthe like are as described in the foregoing.

Also, the upper and lower porous articles 1 of the matrix 6 aresuperposed on the upper and lower surfaces 6 d and 6 e of the matrix 6by forming a hole for passing the projection 6 f of the matrix 6 andfixed by hot welding or the like means. It is desirable that thicknessof the upper and lower porous articles 1 of the matrix 6 isapproximately from 0.5 to 3 mm, because when it is thinner than 0.5 mm,it becomes difficult to absorb irregularity on the surface of thecervical vertebrae C₃ and C₄ or lumbar vertebrae L₄ and L₅ due tocompression deformation so that there is a fear of reducing closelycontacted property with the cervical vertebrae C₃ and C₄ or lumbarvertebrae L₄ and L₅, and when thicker than 3 mm on the other hand, theperiod of time required for the degradation and absorption andsubstitution with a bone tissue becomes long.

It is desirable to contain the aforementioned ossification factors,growth factors, drugs and the like in appropriate amounts in the porousarticle 1 to be filled in the cavity 6 a of the matrix 6 and the porousarticles 1 to be united by superposing on the upper and lower sides ofthe matrix 6, and the wettability may be improved by applying theaforementioned oxidation treatment to the surface of the porous article1.

As shown in FIG. 6, the aforementioned implant material 11 are insertedin a pair of right and left using an insertion jig between the cervicalvertebrae C₃ and C₄ or between the lumbar vertebrae L₄ and L₅, therebyeffecting correction of the distance and posture of the cervicalvertebrae C₃ and C₄ or lumbar vertebrae L₄ and L₅. When the implantmaterial 11 is inserted in this manner, the upper side and lower sideporous articles 1 and 1 of the matrix 6 are compressed by thesandwiching pressure of the cervical vertebrae C₃ and C₄ or lumbarvertebrae L₄ and L₅ and closely contacted to the cervical vertebrae C₃and C₄ or lumbar vertebrae L₄ and L₅ without a gap, and the projections6 f on the upper and lower sides of the matrix 6 cut into the spongybones of the cervical vertebrae C₃ and C₄ or lumbar vertebrae L₄ and L₅at the same time, so that the implant material 11 is fixed withoutcausing displacement and removal and stably arranged due to therectangular prism shape of the matrix 6.

When the implant material 11 is installed by inserting it between thecervical vertebrae C₃ and C₄ or lumbar vertebrae L₄ and L₅ in thismanner, hydrolysis of the matrix 6 which has sufficient strength andtakes the same role of the cortical bone in the living body graduallyprogresses from its surface by contacting with the humor. Also,hydrolysis of the porous article 1 which takes the same role of spongybone quickly progresses from its exposed part by the humor permeatinginto its inner moiety through the continuous pores, and osteoblastpenetrates into the inner moiety of the porous article 1 to conduct andform a bone tissue by the bone conduction ability of the bioceramicspowder, so that the porous article 1 is replaced by the bone tissuewithin a relatively short period of time. Accordingly, the upper, andlower cervical vertebrae C₃ and C₄ or lumbar vertebrae L₄ and L₅ arefused and fixed by this substituted bone tissue. On the other hand, thematrix 6 shows a high compressive strength from the early stage similarto the case of a conventional carbon cage and keeps the strength evenafter bone substitution of the porous article 1, so that it takes agreat role in dynamically fixing the implant material 11 through itscomplete fusion with the cervical vertebrae C₃ and C₄ or lumbarvertebrae L₄ and L₅, and its complete replacement by the bone tissue iscompleted several years (about 5 years) thereafter. At this point oftime, complete solid fusion by living bone has been obtained.

Since the upper side and lower side porous articles 1 of the matrix 6are compressed and thereby closely contacted to the cervical vertebraeC₃ and C₄ or lumbar vertebrae L₄ and L₅ without a gap, and similar tothe case of the aforementioned organic-inorganic complex porous article,the porous article 1 contains from 60 to 90% by weight of a bioceramicspowder having bone conduction ability, has a porosity of from 50 to 90%wherein the continuous pores occupies from 50 to 90% of the total poresand has a pore size of the continuous pores of from roughly 100 toroughly 400 μm, osteoblast can easily penetrate therein so thatconduction formation of a bone tissue is carried out accurately, and theimplant material 11 is fixed by directly bonding to the upper and lowercervical vertebrae C₃ and C₄ or lumbar vertebrae L₄ and L₅ at an earlystage when the bone tissue is conducted and formed on the surface layerof both of the upper and lower sides of the porous article 1 of thematrix 6.

Since both of the matrix 6 and porous article 1 are degraded andabsorbed and replaced by a bone tissue and do not remain in the livingbody as foreign matter, this implant material 11 can wipe out a dangerof exhibiting harmful effects due to its presence in the living body fora prolonged period of time, as is possible in the titanium or carboncages conventionally used as vertebral body fixing materials, and aproblem of causing its sedimentation into the vertebral body due toincompatibility of dynamical characteristics with the living body. Whatis more, since the porous article 1 can be replaced by a bone tissue bycarrying out a histological action similar to a living bone, it is notnecessary to extract an ilium or the like as a transplantation auto-bonefor filling in a cage like the conventional case, and a problem of beinginsufficient in the amount of available auto-bones for transplantationand a problem of complicated treatment at the time of surgical operationafter the extraction can also be wiped out.

Though both of the upper and lower faces 6 d and 6 e of the matrix 6 arehorizontal faces in this implant material 11, the matrix 6 may bechanged into a tapering shape by slanting front side of the upper face 6d downward and slanting front side of the lower face 6 e upward, and animplant material suited for correcting lumber vertebrae to a lordosisposition can be obtained by such a changing.

Also, shape of the matrix 6 is not limited to the aforementionedrectangular prism shape, and it can be made into various shapes suitedfor cervical vertebrae, lumber vertebrae, spinal column and the likeregions to be used. The implant material 12 shown in FIG. 7 is a resultof changing shape of the matrix in such a manner, in which the matrix 6is formed into a cylindrical shape having a cavity 6 a (a cavity whosesection is circular) inside thereof, and an inlet 6 b of a largecircular cavity is formed on each of both terminal faces and an inlet 6b of a small ellipse cavity is formed on its peripheral side in a largenumber arrange in a staggered manner. In addition, the aforementionedorganic-inorganic complex porous article 1 is filled in the cavity 6 aof this matrix 6, and the porous article 1 is partly exposed from eachof the inlets 6 b formed on both terminal faces and peripheral side ofthe matrix 6.

Such an implant material 12 is inserted between cervical vertebrae,lumber vertebrae and the like vertebral bodies in a vertical directionas shown in the drawing, and similar to the case of the aforementionedimplant material 11, the matrix 6 and the porous article 1 are finallyreplaced by a bone tissue to fuse and fix the upper and lower vertebralbodies.

In this connection, as occasion demands, this implant material 12 may bearranged in sideways by forming a male screw on its peripheral side andscrewing it between the upper and lower vertebral bodies.

The implant material 13 shown in FIG. 8 is also a result of changingshape of the matrix, in which the matrix 6 is formed into a low statureannular shape having a small curvature part 6 n, the aforementionedporous article 1 is filled in its inside cavity 6 a, and both of theupper and lower sides of the porous article 1 are exposed from the upperand lower inlets 6 b of said cavity. Though inlet of the cavity is notformed on the peripheral face of this annular shape matrix 6, two ormore inlets of the cavity may be formed as occasion demands. Inaddition, the aforementioned projections for fixing use may be formed onboth of the upper and lower faces of this annular shape matrix 6.

Such an implant material 13 is inserted between cervical vertebrae,lumber vertebrae and the like vertebral bodies with the small curvaturepart 6 n of the matrix 6 being positioned backside, and similar to thecase of the aforementioned implant materials 11 and 12, the matrix 6 andthe porous article 1 are finally replaced by a bone tissue to fuse andfix the upper and lower vertebral bodies.

Each of the aforementioned implant materials 11, 12 and 13 is insertedand arranged as a vertebral body fixing material between cervicalvertebrae, lumber vertebrae and the like vertebral bodies, and it can beused in a bone joint of each region when shape of the matrix 6 isoptionally changed.

The implant material 14 shown in FIG. 9 is embedded in a defect part ofa bone as a substitute for a bone allograft or bone autograft(autogenous graft), it has a block shape organic-inorganic complexporous article 1 and a skin layer 7 which is a biodegradable andbioabsorbable member, and this skin layer 7 is superposed on a part ofthe surface of the porous article 1 and united.

The block shape porous article 1 is identical to the aforementionedorganic-inorganic complex porous article, namely a biodegradable andbioabsorbable porous article having continuous pores, in which abioactive bioceramics powder is substantially uniformly dispersed in abiodegradable and bioabsorbable polymer, wherein a part of thebioceramics powder is exposed to the inner face of the pores or theinner face of the pores and the porous article surface. This porousarticle 1 is prepared by the aforementioned production method of theinvention, and its porosity, pore size of the continuous pores, ratio ofthe continuous pores occupying the total pores, the biodegradable andbioabsorbable polymer, the bioceramics powder, percentage content ofsaid powder and the like are as described in the foregoing.

This porous article 1 takes a role of a spongy bone, its shape is notparticularly limited with the proviso that it has a block shape, and itcan be prepared into various shapes in response to the defect part ofbone to be treated. This porous article 1 may contain the aforementionedossification factors, growth factors, drugs and the like in appropriateamounts, and the wettability may be improved by applying theaforementioned oxidation treatment to the surface of the porous article1 and the surface of the skin layer 7.

The skin layer 7 takes a role of a cortical bone and is a compact andstrong layer comprising a biodegradable and bioabsorbable polymercontaining a bioactive bioceramics powder. According to this implantmaterial 14, the skin layer 7 is superposed on the convex-curved sideface of the block shape porous article 1 and integrated into one body,but it may be arranged by superposing on any one of the other side face,the upper face or the bottom face, or it may be arranged by superposingon two or three or more faces of the porous article 1. In short, thisskin layer 7 may be arranged by partly superposing on the faces of theblock shape porous article 1.

Though thickness of the skin layer 7 is not particularly limited, it isdesirable to optionally set it within the range of from 1.0 to 5.0 mm,by taking into consideration the defect bone part where the implantmaterial 14 is to be embedded. There is a possibility of causinginsufficient strength of the skin layer 7 when it is thinner than 1.0mm, and when thicker than 5.0 mm, it shows disadvantage that a prolongedperiod of time is required for the degradation and absorption of theskin layer 7 and its subsequent substitution with a bone tissue.

Since this skin layer 7 requires a strength larger than that of theporous article 1, crystalline poly-L-lactic acid, polyglycolic acid andthe like are desirably used as the material biodegradable andbioabsorbable polymer, and particularly, a high strength skin layer 7prepared using poly-L-lactic acid having a viscosity average molecularweight of 150,000 or more, preferably approximately from 200,000 to600,000, is suitable.

As the bioceramics powder to be contained in this skin layer 7, all ofthe aforementioned bioactive bioceramics powders to be contained in theporous article 1 can be used, and it is desirable to control itspercentage content within the range of from 10 to 60% by weight. Theskin layer 7 becomes fragile when it exceeds 60% by weight, andformation of bone conduction by the bioceramics powder becomesinsufficient when it is less than 10% by weight.

This skin layer 7 is produced by a method in which a biodegradable andbioabsorbable polymer containing a bioceramics powder is subjected toinjection molding or a molded block of the biodegradable andbioabsorbable polymer containing a bioceramics is subjected to cuttingwork. In the latter method, a skin layer 7 obtained by making a moldedblock into a block in which the polymer molecules and crystals areoriented by a compression molding, forged molding or the like means andthen subjecting this to cutting work is markedly suitable, because ithas a compact quality and its strength is further improved due to thethree dimensionally oriented polymer molecules and crystals. In additionto this, a skin layer prepared by subjecting a stretch-molded moldedblock to a cutting work can also be used.

This implant material 14 is obtained by superposing the skin layer 7prepared by the above method on one convex-curved side face of the blockshape porous article 1 and uniting them in an un-separating form by hotwelding or the like means. The means for integrating the skin layer 7and the porous article 1 into one body is not limited to the hotwelding, and they may be integrated by other means.

When the implant material 14 having the aforementioned construction isembedded in a defect part of a bone as a substitute for a bone allograftor bone autograft (autogenous graft), and the spongy bone moiety of thedefect bone part is filled with the block shape porous article 1,simultaneously filling the cortical bone moiety of the defect bone partwith the skin layer 7, the block shape porous article 1 takes a role ofthe spongy bone and the skin layer 7 having larger strength takes a roleof the cortical bone, thus effecting as if the spongy bone moiety of thedefect bone part is filled with the spongy bone and the cortical bonemoiety is filled with the cortical bone.

When a defect part of a bone is filled with the implant material 14 inthis manner, hydrolysis of the block shape porous article 1 quicklyprogresses because humors penetrate into its inner part through thecontinuous pores, and osteoblast penetrate into the inner part of theporous article 1 to effect conduction formation of a bone tissue by thebone conduction ability of the bioceramics powder. Because of this, theblock shape porous article 1 is replaced by the bone tissue within arelatively short period of time. On the other hand, hydrolysis of theskin layer 7 gradually progresses from the surface falling behind theblock shape porous article 1, and the skin layer 7 keeps sufficientstrength during a period until the block shape porous article 1 isreplaced by a bone tissue in some degree and finally disappears byabsorbed by the bone tissue. Since this implant material 14 does notshow specific living body reaction as described in the foregoing, it canbecome an auto-bone by the penetration and substitution of peripheralliving bones during its nonspecific degradation, absorption anddischarge. That is, since both of the block shape porous article 1 andskin layer 7 are replaced by a bone tissue by their degradation andabsorption and do not remain in the living body as foreign matter, adanger of exhibiting harmful effects after a prolonged period of time ofexistence in the living body, as is possible in conventional implantmaterials made of ceramics, can be wiped out, and a defect part of bonecan be repaired and reconstructed by the replaced bone tissue itself.

Also, since both of the porous article 1 and skin layer 7 of thisimplant material 14 use a biodegradable and bioabsorbable polymer as thematerial, unlike the case of the conventional bone allograft which usesa cadaveric bone as the material, there is no need to worry about ashortage of the material so that it is possible to carry out massproduction of necessary and sufficient amount of the implant materialwithout limitation, and the material can be made into desired shapes andsizes by molding, cutting work and the like.

In addition, the skin layer 7 of this implant material 14 contains abioceramics powder, but being comprised of a biodegradable andbioabsorbable polymer, it does not have a disadvantage of being too hardand brittle unlike the case of a baked ceramics implant material, is noteasily broken due to its toughness and can be heat-deformed whennecessary. Also, the block shape porous article 1 also contains abioceramics powder in a large amount, but being a porous article whichuses a biodegradable and bioabsorbable polymer as the material, evenwhen its porosity is high, it does not show the disadvantage common inthe high magnification porous ceramics, namely tattering fallout offragments even at the time of embedding due to considerable brittleness,and it can be heat-deformed when necessary. Thus, the implant material14 of the invention does not have brittleness, has sufficient practicalstrength, is possible to be heat-deformed and has excellent handlingability.

In this connection, this implant material 14 can be used in manyapplications as a surgical substituent and is particularly effective asprostheses and spacers of cervical vertebrae, lumber vertebrae and thelike vertebral bodies, which are now frequently used but having severalproblems so far revealed.

The implant material 15 shown in FIG. 10 and FIG. 11 is an implantmaterial which is used as prosthetic materials, fillers and the like forthe purpose of recovering, correcting or increasing defect or deformedparts of various skeletal regions such as a skull, a jaw, the face, thechest and the like, and it has an organic-inorganic complex porousarticle 1 and a net-shaped body 8 as a biodegradable and bioabsorbablemember, wherein the porous article 1 is filled in a mesh 8 a of thisnet-shaped body 8 and united therewith.

The net-shaped body 8 of this implant material 15 is a compact andstrong net-shaped body comprising a biodegradable and bioabsorbablepolymer containing a bioactive bioceramics powder, which is obtained byforming the square mesh 8 a on a sheet or plate of a biodegradable andbioabsorbable polymer containing a bioactive bioceramics powder bypunching, cutting work or the like means. Shape of the mesh 8 a is notlimited to a square, and it can be made into circular, lozenge and thelike desired mesh shapes.

It is desirable that opening area of the mesh 8 a is approximately from0.1 to 1.0 cm², and it is desirable that area ratio of the mesh 8 aoccupying the net-shaped body 8 is approximately from 10 to 80%. Also,it is desirable that thickness of the net-shaped body 8 is approximatelyfrom 0.3 to 1.5 mm, and it is desirable that width of thewarp-corresponding part 8 b and weft-corresponding part 8 c of thenet-shaped body 8 is approximately from 2 to 10 mm. When area ratio ofthe mesh 8 a is less than 10%, general strength of the implant material15 is large, but filling amount of the porous article 1 having highhydrolyzing rate to be filled in the mesh 8 a becomes small andoccupying ratio of the net-shaped body 8 having low hydrolyzing ratebecomes large, thus resulting in a prolonged period of time required forthe complete degradation and absorption of the implant material 15 andsubsequent replacement by a bone tissue. On the other hand, when arearatio of the mesh 8 a exceeds 80%, thickness of the net-shaped body 8becomes thinner than 0.3 mm and width of the warp-corresponding part 8 band weft-corresponding part 8 c becomes narrower than 2 mm, strength ofthe net-shaped body 8 is considerably reduced so that it becomesdifficult to obtain an implant material 15 having large strength.

When a net-shaped body 8 having good bending workability is wanted, amelt-molded product of a biodegradable and bioabsorbable polymercontaining a bioceramics powder is once forged at a cold condition (atemperature range of from glass transition temperature of the polymer toits melting temperature) and again forged at a cold condition bychanging the direction (mechanical direction MD), and using this as theaforementioned sheet or plate to be used as the material, a net-shapedbody is prepared by forming the mesh 8 a thereon by punching, cuttingwork or the like means. According to the biodegradable and bioabsorbablepolymer sheet or plate forged twice by changing directions in thismanner, the molecular chain, molecular chain aggregation domain,crystals and the like of the biodegradable and bioabsorbable polymer aremulti-axially oriented or an aggregated structure of a large number ofmulti-axially oriented clusters is formed, so that when this issubjected to bending deformation at an ordinary temperature range (0 to50° C.), the shape is maintained and hardly returned to the originalshape at around the body temperature (30 to 40° C.), and whitening andbreakage hardly occur when the bending deformation is carried out manytimes. Accordingly, since the implant material 15 prepared using thenet-shaped body 8 obtained by forming the mesh 8 a on this sheet orplate has good bending workability, it is possible, for example as shownin FIG. 12, to fix the implant material 15 to a defect part 21 of askull 20 by bending it into a shape identical to the curved face of saiddefect part 21, at ordinary temperature during an operation. In thisconnection, as a sheet or plate to be used as the material of thenet-shaped body 8, those which are monoaxially or biaxially oriented,not oriented or compression molded may be used as a matter of course.

As the material biodegradable and bioabsorbable polymer of thenet-shaped body 8, crystalline poly-L-lactic acid, poly-D-lactic acid,poly-D/L-lactic acid, polyglycolic acid and the like whose safety in theliving body has been confirmed are desirably used. When the strength,hydrolyzing rate and the like of the net-shaped body 8 are taken intoconsideration, such biodegradable and bioabsorbable polymers having aviscosity average molecular weight of 150,000 or more, preferablyapproximately from 200,000 to 600,000, are used.

As the bioceramics powder to be contained in the biodegradable andbioabsorbable polymer of this net-shaped body 8, all of theaforementioned bioactive bioceramics powders to be contained in theporous article 1 can be used, and it is desirable to control itspercentage content within the range of from 10 to 60% by weight.Formation of bone conduction by the bioceramics powder becomesinsufficient when it is less than 10% by weight and the net-shaped body8 becomes fragile when it exceeds 60% by weight.

In this connection, a net-shaped body prepared for example by fusingwarp and weft of a biodegradable and bioabsorbable polymer containing abioceramics powder (flat-sectioned ones are included as the yarn, inaddition to circular-sectioned ones) at their crossing points may beused instead of the aforementioned net-shaped body 8.

On the other hand, the porous article 1 to be filled in each mesh 8 a ofthe aforementioned net-shaped body 8 is the same as the aforementionedorganic-inorganic complex porous article, namely a biodegradable andbioabsorbable porous article having continuous pores, in which abioactive bioceramics powder is substantially uniformly dispersed in abiodegradable and bioabsorbable polymer, wherein a part of thebioceramics powder is exposed to the inner face of the pores or theinner face of the pores and the porous article surface. Porosity of thisporous article 1, pore size of the continuous pores, ratio of thecontinuous pores occupying the total pores, the biodegradable andbioabsorbable polymer, the bioceramics powder, percentage content ofsaid powder and the like are as described in the foregoing.

The aforementioned ossification factors, growth factors, drugs and thelike may be contained in this porous article 1 in appropriate amounts,and the wettability may be improved by applying the aforementionedoxidation treatment to the surface of the porous article 1 andnet-shaped body 8.

As shown in FIG. 12, for example, the implant material 15 having theaforementioned construction is put on the skull 20 covering the defectpart 21 of the skull 20, and several positions of its fringing regionare fixed with a screw 30 comprising a biodegradable and bioabsorbablepolymer. In that case, the implant material 15 is preferably subjectedto bending to match it with the curved face of the defect part 21 of theskull 20.

When the defect part 21 of the skull 20 is covered with the implantmaterial 15 in this manner, hydrolysis of the net-shaped body 8gradually progresses from the surface through its contact with humors,and hydrolysis of the porous article 1 quickly progresses due topenetration of humors into its inner part through the continuous pores.Also, osteoblast penetrate into the inner part of the porous article 1to effect conduction formation of a bone tissue by the bone conductionability of the bioceramics powder contained in the porous article 1, sothat the porous article 1 is replaced by the bone tissue within arelatively short period of time. On the other hand, hydrolysis of thenet-shaped body 8 progresses falling behind the porous article 1, andthe net-shaped body 8 keeps sufficient strength during a period untilthe porous article 1 is replaced by a bone tissue in some degree so thatprotect the defect part 21 of the skull 20. Thereafter, the net-shapedbody 8 also disappears finally by replaced by the bone tissue.

Since both of the porous article 1 and the net-shaped body 8 of thisimplant material 15 are replaced by a bone tissue by their degradationand absorption and do not remain in the living body as foreign matter, adanger of exhibiting harmful effect after a prolonged period of time ofexistence in the living body, as is possible in metal punching platesconventionally used as prosthetic materials of defect parts of bones,can be wiped out, and the defect part 21 of the skull 20 can be repairedand reconstructed by the replaced bone tissue.

In addition, the net-shaped body 8 of this implant material 15 containsa bioceramics powder, but being comprised of a biodegradable andbioabsorbable polymer, it does not have a disadvantage of being too hardand brittle unlike the case of baked compact ceramics, is not easilydefect due to its toughness and can be heat-deformed at ordinarytemperature. In addition, the porous article 1 also contains abioceramics powder in a large amount, but since it uses a biodegradableand bioabsorbable polymer as the matrix, even when its porosity is high,it does not show the problem common in high magnification porousceramics which cause tattering fallout of fragments even during theirfilling due to considerable brittleness, and it can be heat-deformedwhen necessary. Thus, the implant material 15 does not have brittleness,has sufficient practical strength, is possible to be heat-deformed andhas excellent handling ability.

It was able to make this implant material 15 as a living bone substituteof a high area and less material by making a net-shaped body taking arole of high strength cortical bone and by increasing porosity of theporous article which takes a role of a spongy bone, and being acombination of the net-shaped body and porous article, the total amountof their materials was restricted to a level as small as possible, sothat this is an implant material containing small contents to be treatedby the living body during its degradation absorption process and havingexcellent biocompatibility.

In this connection, in addition to the application example shown in FIG.12, this implant material 15 is used for the restoration andreconstruction of relatively large defect parts of bones, such asfilling of depressed fracture of central face and filling of parts afterextraction of foci of bone tumor and the like, and is also used as abase material for bone extension.

According to the aforementioned implant material 15 which is a combinedtype of the porous article 1 and the net-shaped body 8, not only fillingof the porous article 1 into the mesh 8 a of net-shaped body 8, but alsoconstruction of a structure by further arranging the porous article 1 inlayers on one side or both sides of the net-shaped body 8 is a leadingembodiment. FIG. 13 and FIG. 14 show implant materials 16 and 17 of suchan embodiment, in which in the case of the implant material 16, theaforementioned organic-inorganic complex porous article 1 is arranged ina layer shape on one side of the aforementioned implant material 15, andin the case of the implant material 17, the aforementionedorganic-inorganic complex porous article 1 is arranged in a layer shapeon both sides of the aforementioned implant material 15.

The layer shape porous article 1 is identical to the aforementionedorganic-inorganic complex porous article 1, which is prepared in a layerform (sheet form) by the aforementioned production method of theinvention. This layer shape porous article 1 is integrally laminated onone side or both sides of the implant material 15 by heat fusion or thelike means. Thickness of this layer shape porous article 1 is notparticularly limited, but when its close adhesion to peripheral bone ofa defect bone part and a period required for its degradation andabsorption and subsequent substitution with a bone tissue are taken intoconsideration, it is desirable to set it to a thickness of approximatelyfrom 0.5 to 3 mm.

Since a bone tissue is formed on one side or both sides of such implantmaterials 16 and 17 almost uniformly during a relatively short period oftime, facial restoration and reconstruction of the defect bone part arequickly carried out. Also, since the porous article 1 arranged in alayer form is closely contacted to the peripheral bone of the defectbone part by taking a role as a cushion material, and osteoblast easilypenetrates into the layer form porous article 1, a bone tissue isconducted and formed on the surface layer region of the porous article 1in an early stage, and the implant material 16 or 17 is directly bondedto the peripheral bone of the defect bone part and strongly fixed.

In addition, according to the aforementioned implant material 15 whichis a combined type of the porous article 1 and the net-shaped body 8,construction of a structure by concave-curving or convex-curving thenet-shaped body 8 and further arranging the porous article 1 insidethereof is also a leading embodiment. FIG. 15 shows an implant material18 of such an embodiment, and in this implant material 18, the net-shapebody 8 of the aforementioned implant material 15 is concave-curved intoU-shape, and a porous article 1 identical to the porous article 1 filledin its mesh is also filled in inside of the net-shaped body 8, namelyinside of the concave curve. As the net-shaped body 8, a net-shaped bodyprepared by forming meshes on the aforementioned biodegradable andbioabsorbable polymer sheet or plate, forged twice by changing itsmechanical direction to provide good bending workability, isparticularly preferably used because of its high mechanical strength andits possibility to carry out bending at ordinary temperature.

Such an implant material 18 is prepared into such a size that it can beembedded and filled into defect parts of, for example, jaw bone and thelike, and used for the restoration and reconstruction of a defect partof jaw bone as shown in FIG. 12 by an imaginary line. In addition, withthe aim of filling and regenerating a living bone lost by an accident ora cancer, this can also be used suitably for the restoration andreconstruction of not only defect parts of a skull, a central face andan upper jaw, a lower jaw or the like jaw face, but also defect parts ofother large bones in the field of orthopedic surgery.

In this connection, though the net-shaped body 8 of the aforementionedimplant material 18 is concave-curved into U-shape, the implant material18 may be prepared by concave-curving or convex-curving the net-shapedbody 8 into a shape which corresponds and matches to a defect bone partto be reconstructed, and filling the porous article 1 in its inside, andas occasion demands, the porous article 1 may be further arranged in alayer form on the outside of the implant material 18. In addition, itmay be made into an implant material having a structure in which thenet-shaped body 8 is folded up and the porous article 1 is also filledbetween the folded net-shaped body 8, or it may be made into an implantmaterial having a sandwich structure in which two sheets of the implantmaterial 15 are piled up and a layer form porous article 1 is interposedbetween them.

FIG. 16 and FIG. 17 show an implant material 19 for artificial cartilageuse. This implant material 19 for artificial cartilage use has theaforementioned organic-inorganic complex porous article 1, a corematerial 9 as a bio-non-absorbable member and a pin 22 for fixing use asa biodegradable and bioabsorbable member, in which a porous article 1 islaminated and united on both upper and lower sides of thebio-non-absorbable core material 9, and the tip of the pin 22 for fixinguse is protruded from the surface of the porous article 1.

This implant material 19 for artificial cartilage use is formed into ablock shape having a flat shape which is roughly square at the head andround at the foot as a result of uniting a rectangle with a half circleas shown in FIG. 16, and is suitably used as an artificialintervertebral disk.

The core material 9 comprises a texture structure body in which organicfibers are made into a three dimensional woven texture or knittedtexture or a complex texture thereof and has mechanical strength andflexibility similar to those of intervertebral disk or the likecartilage, and its deformation is markedly biomimetic (living bodymimicry). The texture structure body of this core material 9 is similarto the texture structure body described in Japanese Patent ApplicationNo. Hei.-6-254515 already applied by the present applicant, and when itsgeometrical shape is represented by the number of dimensions and thenumber of its fiber arrangement directions is represented by the numberof axes, a structural body comprising a multiaxis-three dimensionaltexture of three axes or more is suitably employed.

The three axes-three dimensional texture is a product in which fibers inlengthwise, breadthwise and vertical three axis directions are woven orknitted three-dimensionally, and the typical shape of the structuralbody is a bulk form having a thickness (plate form or block form) likethe case of the aforementioned core material 9, but it is possible tomake into a cylindrical shape or honeycomb shape. Based on thedifference in textures, this three axes-three dimensional texture isclassified into an orthogonal texture, a non-orthogonal texture, a lenotexture, a cylindrical texture and the like. Also, regarding astructural body of a multiaxis-three dimensional texture of four axes ormore, isotropy in strength of the structural body can be improved byarranging 4, 5, 6, 7, 9, 11 axes and the like multiple axis directions.By selecting these conditions, a core material which is more biomimeticand more closely resembled to the cartilage tissues of the living bodycan be obtained.

It is desirable that porosity of the inner moiety of the core material 9comprising the aforementioned texture structure body is within the rangeof from 20 to 90%, because when it is less than 20%, the core material 9becomes compact to spoil its flexibility and deforming property andtherefore becomes unsatisfactory as the core material of an implantmaterial for artificial cartilage, and when it exceeds 90%, compressivestrength and shape keeping property of the core material 9 are reducedso that it is unsuitable as the core material of an implant material forartificial cartilage.

As the organic fibers which constitute the core material 9, bio-inactivesynthetic resin fibers such as fibers of polyethylene, polypropylene,polytetrafluoroethylene and the like, coated fibers bio-inactivated bycoating organic core fibers with the aforementioned bio-inactive resin,and the like are preferably used. Particularly, coated fibers having adiameter of approximately from 0.2 to 0.5 mm, prepared by coating corefibers (twine) of an ultra-high molecular weight polyethylene with thecoating of a straight chain low density polyethylene, are the mostappropriate fibers in view of strength, hardness, flexibility, easyweaving and knitting and the like. Alternatively, fibers havingbioactivity (e.g., having bone conduction or induction ability) can alsobe selected.

In this connection, the texture structure body constituting the corematerial 9 is disclosed in detail in the aforementioned Japanese PatentApplication No. Hei.-6-254515, so that descriptions further than thisare omitted.

The porous article 1 to be laminated on both upper and lower sides ofthe core material 9 is the same as the aforementioned organic-inorganiccomplex porous article, namely a biodegradable and bioabsorbable porousarticle having continuous pores, in which a bioactive bioceramics powderis substantially uniformly dispersed in a biodegradable andbioabsorbable polymer, wherein a part of the bioceramics powder isexposed to the inner face of the pores or the inner face of the poresand the porous article surface. This porous article 1 is prepared by theaforementioned production method of the invention, and its porosity,pore size of the continuous pores, ratio of the continuous poresoccupying the total pores, the biodegradable and bioabsorbable polymer,the bioceramics powder, percentage content of said powder and the likeare as described in the foregoing.

Since this porous article 1 has a role as a spacer, when this porousarticle 1 is laminated on both sides of the core material 9 and whenthis implant material 16 is inserted between cervical vertebrae, lumbarvertebrae or the like vertebral bodies (cf. cervical vertebrae C₃ and C₄or lumbar vertebrae L₄ and L₅ in FIG. 6), the porous article 1 iscompression-deformed by the clipping pressure of the upper and lowervertebral bodies and closely contacted with the vertebral bodies withouta gap, and accompanied by the hydrolysis of the porous article 1 due toits contact with humors, a bone tissue is conducted and formed in theinner portion of the porous article 1 by the bone conduction ability ofthe bioceramics powder, and the porous article 1 is replaced by the bonetissue within a relatively short period of time, and the vertebralbodies and the core material 9 are directly bonded. In this case, whenthe surface layer is bio-activated by spraying a bioceramics powder tothe surface of the core material 9, the conducted living bone binds tothis activated surface layer, so that direct bonding of the vertebralbodies and the core material 9 is effected within a relatively shortperiod of time and the strength is also maintained. In addition, when abone induction factor is contained in this porous article 1, boneinduction is exhibited so that it is more effective.

It is desirable to set thickness of this porous article 1 toapproximately from 0.5 to 3 mm, because when it is thinner than 0.5 mm,it becomes difficult to absorb irregularity on the surface of thevertebral bodies due to compression deformation so that there is apossibility of reducing closely contacted property with the vertebralbodies, and when thicker than 3 mm on the other hand, the period of timerequired for the degradation and absorption and substitution with a bonetissue becomes long. Also, as shown in FIG. 17, it is desirable tolaminate this porous article 1 in such a manner that about half of itsthickness is buried in the core material 9 and thereby to surround theporous article 1 with the peripheral part of the core material 9,because abrasion of the periphery of the porous article 1 can beinhibited by such an arrangement.

In this connection, appropriate amounts of the aforementionedossification factors, growth factors, drugs and the like may becontained in this porous article 1, and in that case, ossification inthe inner moiety of the porous article 1 is considerably accelerated anddirect binding of the core material 9 with vertebral bodies isestablished effectively in a early stage. In addition, effects of thepenetration and growth of osteoblast to be proliferated may be increasedby applying the aforementioned oxidation treatment to the surface of theporous article 1 and thereby improving its wettability.

The fixing pin 22 passes through the aforementioned core material 9 andporous articles 1 on both sides thereof, and both termini of the pin areprojected from the porous articles 1. In case that such a fixing pin 22is present, when this implant material 19 is inserted between upper andlower vertebral bodies, both termini of the fixing pin 22 projectingfrom the porous articles 1 cut into the contacting faces of thevertebral bodies by the clipping pressure of the upper and lowervertebral bodies, so that the implant material 19 is fixed between thevertebral bodies and does not generate misplacement.

It is desirable that the number of the fixing pin 22 is two or more,most preferably 3 as shown in the drawing, and in that case, there is anadvantage in that this material can be stably installed between theupper and lower vertebral bodies effected by the three-point support. Itis desirable to form both termini of the fixing pin 22 into a conical orthe like pointed shape, and it is desirable to set diameter of the pin22 to approximately from 1 to 3 mm in order to ensure its strength. Inaddition, it is desirable to set the projecting size of both termini ofthe fixing pin 22 to approximately from 0.3 to 2 mm.

Since a large clipping pressure is applied to the fixing pin 22 from theupper and lower vertebral bodies at the beginning when the implantmaterial 19 is inserted between the vertebral bodies, a fixing pinhaving large strength is required. Accordingly, it is desirable toproduce this fixing pin 22 using crystalline polylactic acid,polyglycolic acid and the like biodegradable and bioabsorbable polymershaving a viscosity average molecular weight of 150,000 or more,preferably approximately from 200,000 to 600,000, and the use of thesepolymers further mixed with a bioactive bioceramics powder is alsodesirable. In addition, as occasion demands, the strength may beimproved through the orientation of polymer molecules by compressionmolding, forged molding, stretching or the like method.

When the implant material 19 for artificial cartilage of theaforementioned construction is installed as an artificial intervertebraldisk between upper and lower vertebral bodies, both termini of thefixing pin 22 projecting from the surface of the porous articles 1 cutinto the contacting faces of the vertebral bodies as already describedin the foregoing, so that the implant material 19 is fixed between thevertebral bodies and does not generate displacement. Accordingly, sincefixation of living body materials using auxiliary fixing tools and thelike becomes unnecessary, operations can be carried out easily. Inaddition, when the implant material 19 is installed between vertebralbodies in this manner, the porous article 1 on the surface of the corematerial 9 is compressed by the clipping pressure of the upper and lowervertebral bodies and closely contacted with the vertebral bodies withouta gap, and as degradation and absorption of the porous article 1advance, a bone tissue is conducted and formed in the inner portion ofthe porous article 1, so that the porous article 1 is replaced by thebone tissue within a relatively short period of time and the vertebralbodies and the core material 9 are directly bonded. However, since thecore material 9 is a bio-inactive synthetic resin fiber, the bone tissueis not conducted and formed inside thereof, and it keeps itsflexibility. Since this core material 9 comprises a texture structurebody prepared by converting organic fibers into a multi-axial threedimensional weave texture or knit texture of three axes or more or acomplex texture thereof as already described, it has mechanical strengthand flexibility similar to those of intervertebral disk or the likecartilage, and its deformation is relatively easy, so that it canperform a role of the intervertebral disk showing almost the samebehavior of the intervertebral disk. In addition, the fixing pin 22 isalso degraded and absorbed by the living body within a relatively shortperiod of time so that it does not remain.

As described in the above, regarding this implant material 19 forartificial cartilage, the core material 9 is biomimetic and its behaviorclosely resembles cartilage tissues, and in addition to this, it hasdirect binding ability with and early stage independence from vertebralbody and the like bone end-plates, its own side slip and rolling isprevented by the tip of the fixing pin 22 stuck into the bone tissue,and the porous article 1 binds to directly to the bone tissue andhistologically integrated into one body. Accordingly, this implantmaterial 19 for artificial cartilage can dissolve all of the alreadydescribed disadvantages involved in the conventional independent typeartificial intervertebral disk of sandwich structure.

In this connection, in the aforementioned implant material 19 forartificial cartilage, the porous article 1 is laminated on both sides ofthe core material 9 and both termini of the fixing pin 22 are protrudedfrom the porous article 1, it may be made into a construction in whichthe porous article 1 is laminated on one side of the core material 9 andone side tip of the fixing pin 22 is protruded. Since an implantmaterial for artificial cartilage of such a construction can fix its oneside to one of the vertebral bodies with the fixing pin 22, the fixingstrength is reduced but displacement of the implant material 19 can beprevented. Also, thickness of the porous article 1 may be increasedgradually from its square head part toward round foot part, and whenarranged in this manner, the space between the upper and lower vertebralbodies becomes slightly narrow in the head side and slightly broad inthe foot side so that it becomes an implant material which can beinstalled by exactly fitting to said space. In addition, as occasiondemands, instead of the fixing pin 22 to be passed through, a shortfixing pin may be embedded into the surface layer region of the corematerial 9 and the pin tip may be protruded from the porous article 1.

Thus, an implant material 19 for artificial intervertebral disk has beendescribed, but it goes without saying that it becomes implant materialsfor semilunar disk and various types of joint cartilage other than theartificial intervertebral disk when its shape is optionally changed.

While the invention has been described in detail and with reference tospecific embodiments thereof, it will be apparent to one skilled in theart that various changes and modifications can be made therein withoutdeparting from the spirit and scope of the invention.

This application is based on Japanese patent application filed on Nov.27, 2001 (Japanese Patent Application No. 2001-360766), Japanese patentapplication filed on Dec. 3, 2001 (Japanese Patent Application No.2001-368558), Japanese patent application filed on Feb. 20, 2002(Japanese Patent Application No. 2002-043137), Japanese patentapplication filed on Aug. 23, 2002 (Japanese Patent Application No.2002-242800) and Japanese patent application filed on Sep. 30, 2002(Japanese Patent Application No. 2002-285934), the entire contentsthereof being hereby incorporated by reference.

INDUSTRIAL APPLICABILITY

The implant material of the invention is practically used as ascaffolding for the reconstruction of living bone tissue, a prostheticmaterial, a bone filler, an inclusion between other implant and a livingbone tissue, a substitute for spongy bone, a carrier for sustained drugrelease and the like. Also, by uniting with other biodegradable andbioabsorbable member and/or bio-non-absorbable member, the implantmaterial of the invention is practically used as various bone fixingmaterials, a vertebral body fixing material, various spacers betweenliving bones, a defect bone part filling material, a prosthetic materialor filler, an artificial cartilage material and the like.

The invention claimed is:
 1. An implant material comprising a bioactiveorganic-inorganic complex porous article which is a biodegradable andbioabsorbable bioactive porous article in which a bioactive bioceramicspowder is uniformly dispersed in a biodegradable and bioabsorbablepolymer, wherein the bioactive organic-inorganic complex porous articleis obtained by forming a nonwoven fabric-like fiber aggregate from amixed solution of a biodegradable and bioabsorbable polymer and abioactive bioceramics powder, forming the nonwoven fabric-like fiberaggregate into a porous fiber aggregate molding by compression-moldingunder heating, soaking the fiber aggregate molding in a volatilesolvent, and then removing said solvent, wherein the mixed solution isprepared by dissolving a biodegradable and bioabsorbable polymer in avolatile solvent and dispersing a bioactive bioceramics powder in theresulting solution.
 2. The implant material described in claim 1,wherein porosity of the porous article is from 50 to 90%, and thecontinuous pores occupy from 50 to 90% of the total pores.
 3. Theimplant material described in claim 1, wherein the pore size of thecontinuous pores of the aforementioned porous article is approximatelyfrom 100 to 400 μm.
 4. The implant material described in claim 1,wherein the biodegradable and bioabsorbable polymer of the porousarticle is any one of a totally absorbable poly-D,L-lactic acid, a blockcopolymer of L-lactic acid with D,L-lactic acid, a copolymer of lacticacid with glycolic acid, a copolymer of lactic acid with p-dioxanone anda block copolymer of lactic acid with ethylene glycol.
 5. The implantmaterial described in claim 1, wherein the percentage content ofbioceramics powder of the porous article is from 60 to 90% by weight. 6.The implant material described in claim 1, wherein the percentagecontent of bioceramics powder of the porous article is from 50 to 85% byvolume.
 7. The implant material described in claim 1, wherein an averageparticle size of the bioceramics powder contained in the porous articleis from 0.2 to
 10. 8. The implant material described in claim 1, whereinthe bioceramics powder contained in the porous article is any one ofpowders of totally absorbable un-calcined or un-sintered hydroxyapatite,dicalcium phosphate, tricalcium phosphate, tetracalcium phosphate,octacalcium phosphate, calcite, ceravital, diopside and natural coral.9. The implant material described in claim 1, wherein compressivestrength of the porous article is from 1 to 5 MPa.
 10. The implantmaterial described in claim 1, wherein an oxidation treatment is appliedto the porous article.
 11. The implant material described in claim 1,wherein the porous article has a three dimensional solid shape having athickness of from 1 to 50 mm.
 12. A method for producing an implantmaterial comprising an organic-inorganic complex porous article of claim1, comprising (a) dissolving a biodegradable and bioabsorbable polymerin a volatile solvent and dispersing a bioactive bioceramics powdertherein to form a mixed solution, (b) forming a nonwoven fabric-likefiber aggregate from the mixed solution, (c) compression-molding thenonwoven fabric-like fiber aggregate under heat to form a porous fiberaggregate molding, (d) soaking the porous fiber aggregate molding in thevolatile solvent, and (e) removing the solvent, thereby producing animplant material comprising an organic-inorganic complex porous article.13. The method described in claim 12, wherein the compression-molding of(c) comprises two steps: (i) solidifying the nonwoven fabric-like fiberaggregate under heating and compression to prepare a preliminarilymolded product, and (ii) subjecting the preliminarily molded product tocompression molding under a pressure higher than the pressure used toprepare the preliminarily molded product, thereby preparing the porousfiber aggregate molding.
 14. The production method described in claim12, wherein in the soaking of (d), the porous fiber aggregate molding ispacked in a mold having a predetermined shape and a large number ofpores prior to exposure to the solvent, and soaked in the solvent whilemaintaining the shape of the mold.